# Patent

## Title
Conjugates of biologically active polypeptides having an increased in vivo half-life

## Abstract

Disclosed are biologically active protein conjugates that comprise a biologically active polypeptide coupled via a peptide bond to a polypeptide comprising from 2 to about 500 units of a repeating peptide motif, wherein the biologically active protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide or protein. Also disclosed are methods of making and using the conjugated proteins, as well as methods for determining whether a given conjugate exhibits a modified half life relative to the intrinsic half life of the unconjugated polypeptide.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is a continuation of U.S. application Ser. No. 12/251,324, filed Oct. 14, 2008, which is a continuation of U.S. application Ser. No. 11/880,377, filed Jul. 20, 2007, which is a continuation of International Application No. PCT/US2006/002501, filed Jan. 25, 2006, published in English, which claims priority under 35 U.S.C. 119 (e) from U.S. Provisional Application No. 60/712,585, filed Aug. 30, 2005 and U.S. Provisional Application No. 60/647,119, filed Jan. 25, 2005, all of which are incorporated by reference herein.


TECHNICAL FIELD
This invention relates generally to biologically active proteins, and more specifically to altering the haft-life of biologically active proteins.
SEQUENCE LISTING
The sequence listing associated with this application is provided in text format in lieu of a paper copy and is hereby incorporated by reference into the specification. The name of the text file containing the sequence listing is 38616_Sequence_Substitute—2012-05-01.txt. The text file is 2.08 MB; was created on May 1, 2012; and has been submitted via EFS-Web.
BACKGROUND OF THE INVENTION
Biologically active proteins often have undesirable half-lives when administered as human therapeutics. Their intrinsic half-lives impose administration schedules and dosing regimens that often result in less than optimal therapeutic efficacy, compliance problems and patient inconvenience.
In the manufacture of biologically active proteins for human therapeutics, the extension of the half-life of biologically active proteins has been attempted through physical means (e.g., altered route of administration, nanoparticle encapsulation and liposomal entrapment), chemical modification (e.g., emulsions, pegylation and hyperglycosylation) and genetic modification (e.g., modification of primary protein structure, polymer tags, human serum albumin fusion, incorporation of post-translational modification). See, for example, Lord, et al., Clin. Cancer Res. 7:2085-2090 (2001), and van Der Auwera, et al., Am. J. Hematol. 66:245-251 (2001). However, such approaches have resulted in other problems. Extension of biologically active protein half-life through physical means often introduces increased drug substance complexity with costly and time-consuming additional downstream processes during manufacturing. Chemical modification may alter the biological activity or safety profile of the biologically active protein. Where biologically active proteins are made via recombinant DNA synthesis methodology, the effect of the genetic modification on protein yield and purity in the particular cellular expression systems issues needs to be assessed for its intended use.
Accordingly, there is a need for other approaches for modifying the intrinsic half-life of biologically active proteins.
SUMMARY OF THE INVENTION
One aspect of the present invention is directed to a protein conjugate comprising a biologically active polypeptide coupled via a peptide bond to a polypeptide (amino acid extension) that comprises from 2 to about 500 repeating units of a peptide motif. The motif comprises a major constituent and a minor constituent, in which the major constituent is two or more residues of one amino acid selected from Gly (G), Asn (N) and Gln (Q), and the minor constituent is one or more residues of one amino acid selected from Ala (A), Ser (S), Thr (T), Asp (D), Gln (Q), Glu (E), His (H) and Asn (N), with the proviso that none of the amino acids is present in both the major constituent and said minor constituent, wherein the plasma half-life of the conjugate is modified relative to the intrinsic half-life of the unconjugated biologically active polypeptide. The term “modified”, as used herein, refers to an increased or a decreased half-life relative to the plasma half-life of the unconjugated biologically active polypeptide or protein itself (i.e., the intrinsic half life). By the phrase “intrinsic half-life” it is meant the half-life of the native biologically active polypeptide or the half-life of the polypeptide in unconjugated form (thus including recombinant forms of the native polypeptide).
In some embodiments, the peptide motif comprises 3-6 amino acid residues (i.e., 3, 4, 5 or 6). In some embodiments, wherein the peptide motif contains 5 or 6 amino acid residues, the minor constituent comprises 1 amino acid residue of said peptide. In some embodiments, the peptide motif has a sequence consisting of N and T amino acid residues, N and E amino acid residues, Q and S amino acid residues, or N and Q amino acid residues. In some embodiments, the amino acid extension is N-terminal with respect to said biologically active polypeptide; in some embodiments, it is C-terminal with respect to said biologically active polypeptide; and in other embodiments, it is situated at both the N and C-terminus with respect to said biologically active polypeptide. In some embodiments, the biologically active polypeptide is a cytokine (e.g., granulocyte colony stimulating factor (G-CSF), human growth hormone (SEQ ID NO:2472), or an interferon such as a beta-interferon (SEQ ID NO:2468) or a gamma-interferon (SEQ ID NO:2470)), an antibody, antibody fragment, proteolytic antibody fragment or domain, single chain antibody, genetically or chemically optimized antibody or fragment thereof, a soluble gp 120 or gp 160 glycoprotein, a coagulation factor, a soluble receptor such as a tumor necrosis factor (TNF)-α type II receptor (SEQ ID NO:2464), a therapeutic enzyme or erythropoietin (EPO; SEQ ID NOs:2452, 2480 and 2481). In some embodiments, the protein conjugate has a modified half-life that is decreased relative to the intrinsic half-life of the unconjugated biologically active polypeptide, e.g., wherein said biologically active polypeptide comprises a recombinant activated protein C or a recombinant Factor VII.
Another aspect of the present invention is directed to a composition comprising the protein conjugate and a carrier. In some embodiments, the composition is a pharmaceutical composition and the carrier is a pharmaceutically acceptable carrier.
Another aspect of the present invention is directed to a chimeric DNA molecule that encodes the protein conjugate described above, as well as a vector, together comprising the chimeric DNA molecule, and a cell transformed with the chimeric DNA molecule or a vector containing it. In some embodiments, the vector is a plasmid, e.g., pCE2. In some embodiments, the cell is a mammalian cell e.g., a Chinese hamster ovary (CHO) cell, or a bacterium e.g., E. coli, or yeast.
Yet another aspect of the present invention is directed to a method of making a biologically active protein conjugate comprising a biologically active polypeptide coupled via peptide bond to a polypeptide comprising from 2 to about 500 units of a peptide comprising as a major constituent, two or more residues of one amino acid selected from Gly (G), Asn (N) and Gln (Q), and as a minor constituent, one or more residues of one amino acid selected from Ala (A), Ser (S), Thr (T), Asp (D), Gln (Q), Glu (E), His (H) and Asn (N), provided that none of said amino acids is present in said major constituent and said minor constituent, such that said biologically active protein has a modified plasma half-life compared to intrinsic half-life of the unconjugated biologically active polypeptide, said method comprising: culturing a cell transformed with a chimeric DNA molecule encoding said protein conjugate under conditions whereby said DNA is expressed, thereby producing said protein conjugate; and extracting an expression product of said chimeric DNA molecule from said cell.
A further aspect of the present invention is directed to a method of determining whether a given protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide, comprising: a) preparing a protein conjugate comprising a biologically active polypeptide coupled via a peptide bond to a polypeptide that comprises from 2 to about 500 repeating units of a peptide motif, wherein the motif comprises a major constituent and a minor constituent, in which the major constituent comprises or consists of two or more residues of one amino acid selected from the group consisting of Gly (G), Asn (N) and Gln (Q), and the minor constituent comprises or consists of one or more residues of one amino acid selected from the group consisting of Ala (A), See (S), Thr (T), Asp (D), Gln (Q), Glu (E), His (H) and Asn (N), wherein none of the amino acids is present in both the major constituent and said minor constituent, and b) testing the protein conjugate to determine whether the protein conjugate has a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation of the PHO×pBSK vector.
FIG. 2 is a schematic representation of the RHO-G-CSF-NN×pBSK vector.
FIG. 3 is a schematic representation of the PHO-G-CSF-NNT65×pBSK, vector (NNT65 disclosed as SEQ ID NO: 1).
FIG. 4 is a schematic representation of the PHO-G-CSF-NNT155×pBSK vector (NNT155 disclosed as SEQ ID NO: 2).
FIG. 5 is a schematic representation of the PHO-G-CSF-NNT155×pCE2 vector (NNT155 disclosed as SEQ ID NO: 2).
FIG. 6 is a Western blot of several different G-CSF-polypeptide conjugates and unconjugated G-CSF, NNT65, NNT155 and NNNNNTNN61 disclosed as SEQ ID NOS: 1-3, respectively.
FIG. 7 is a Western blot of several different G-CSF-polypeptide conjugates and unconjugated G-CSF that were treated with PNGase F prior to electrophoresis. NNT65, NNT155 and NNNNNTNN61 disclosed as SEQ ID NOS: 1-3, respectively.
FIG. 8 is a Western blot of the G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) and G-CSF-NNT65 (NNT65 disclosed as SEQ ID NO: 1) constructs (in duplicate) that were expressed in CHOK1 cells grow in PROCHO4-CDM media.



DETAILED DESCRIPTION
As used herein, the term “polypeptide” means a polymer of amino acids having no specific length, unless otherwise specified. Thus, peptides and proteins are included in the definition of “polypeptide” and these terms are used interchangeably throughout the specification, as well as in the claims. The term “polypeptide” does not exclude post-translational modifications, such as polypeptides having covalent attachment of glycosyl groups, acetyl groups, phosphate groups, lipid groups, hydroxylation of proline or lysine, and the like. Also encompassed by this definition of “polypeptide” are homologs thereof.
The term “purified” as used herein means that the biologically active protein conjugate has been purified to a level adequate for its intended use.
The present invention is directed, in a general aspect, to a protein conjugate comprising a biologically active polypeptide coupled via peptide bond to a polypeptide that comprises from 2 to about 500 units of a peptide motif that contains a major constituent of two or more residues of one amino acid selected from Gly (G), Asn (N) and Gln (Q), and a minor constituent of one or more residues of one amino acid selected from Ala (A), Ser (S), Thr (T), Asp (D), Gln (Q), Glu (E), His (H) and Asn (N), provided that none of the amino acids is present as both a major constituent and minor constituent. The protein conjugates of the present invention have a plasma half-life greater than the corresponding unconjugated biologically active polypeptide or protein.
The repeating unit of the motif generally contains 3-7 (3, 4, 5, 6 or 7) amino acid residues. Representative peptide motifs having N (Asn) as the major constituent are described in Table 1.
Representative peptide motifs having G (Gly) as the major constituent are described in Table 2.
Representative peptide motifs having Q (Gln) as the major constituent are described in Table 3.
The number of the peptide motifs ranges from 2 to about 500. Thus, the motifs including the specific peptide motifs set forth herein, may be present in the polypeptide in the following number of units: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499 and 500 (thus including any subrange thereof).
As described above, the polypeptide conjugated to the biologically active polypeptide may also be referred to as an amino acid or polyamino extension (hereinafter “amino acid extension”) of the biologically active polypeptide. The amino acid extension may be situated at the N-terminus, at the C-terminus or at both the N and C-termini, with respect to the biologically active polypeptide sequence.
Without intending to be bound by theory, Applicants believe that the amino acid extensions do not adopt stable conformations and as such, do not interfere with or otherwise influence the activity of the protein. Also, limiting the amino acid extension to two different amino acids is believed to reduce the chemical complexity of the amino acid extension, which helps minimize the potential for immunogenicity, as well as allowing for the modulation of physicochemical properties far more extensively than is possible through the use of just one type or kind of amino acid.
Broadly, the biologically active polypeptide includes any protein (including native polypeptides (i.e., as they exist in vivo)) or polypeptides produced recombinantly, such as recombinant human G-CSF (rh-G-CSF; SEQ ID NO:2450) for which a modified plasma half-life would be desirable from some standpoint, particularly from a therapeutic standpoint, meaning that when delivered to a vertebrate organism, treats, e.g., cures, ameliorates, or lessens the symptoms of, a given disease in that vertebrate, or alternatively, prolongs the life of the vertebrate by slowing the progress of a terminal disease. Types of biologically active proteins include cytokines, chemokines, lymphokines, ligands, receptors, hormones, apoptosis-inducing polypeptides, enzymes, antibodies and antibody fragments, and growth factors. Examples of receptors include TNF type I receptor, SEQ ID NO:2466, IL-1 receptor type II, IL-1 receptor antagonist, IL-4 receptor and any chemically or genetically modified soluble receptors. Examples of enzymes include activated protein C, factor VII, collagenase (e.g., marketed by Advance Biofactures Corporation under the name SANTYL®); agalsidase-beta (e.g., marketed by Genzyme under the name FABRAZYME®); dornase-alpha (e.g., marketed by Genentech under the name PULMOZYME®); alteplase (e.g., marketed by Genentech under the name ACTIVASE®); pegylated-asparaginase (e.g., marketed by Enzon under the name ONCASPAR®); asparaginase (e.g., marketed by Merck under the name ELSPAR®); and imiglucerase (e.g., marketed by Genzyme under the name CEREDASE®). Examples of specific polypeptides or proteins include, but are not limited to granulocyte macrophage colony stimulating factor (GM-CSF; SEQ ID NO:2462), granulocyte colony stimulating factor (G-CSF; SEQ ID NO:2450), macrophage colony stimulating factor (M-CSF; SEQ ID NOs: 2454, 2456, 2458, and 2460), colony stimulating factor (CSF), interferon beta (IFN-β, SEQ ID NO:2468), interferon gamma (IFNγ, SEQ ID NO:2472), interferon gamma inducing factor I (IGIF), transforming growth factor beta (TGF-β), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), macrophage inflammatory proteins (e.g., MIP-1-α and MIP-1-β), Leishmania elongation initiating factor (LEIF), platelet derived growth factor (PDGF), tumor necrosis factor (TNF), growth factors, e.g., epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor, (FGF), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-2 (NT-2), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), neurotrophin-5 (NT-5), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), TNF α type II receptor (SEQ ID NO:2464), erythropoietin (EPO; SEQ ID NOs:2452, 2480 and 2481), insulin and soluble glycoproteins e.g., gp120 and gp160 glycoproteins. The gp120 glycoprotein is a human immunodeficiency virus (HIV) envelope protein, and the gp160 glycoprotein is a known precursor to the gp 120 glycoprotein.
In some embodiments, it is desirable to modify the half-life of a biologically active polypeptide such that it is decreased relative to the intrinsic half life, is desirable. Such embodiments include recombinant activated protein C (e.g., marketed by Eli Lilly under the name XIGRIS®) and Recombinant Factor VII (marketed by Novo Nordisk under the name NOVOSEVEN®).
Biologically active polypeptides may be used to treat diseases such as Parkinson's disease, cancer, and heart disease. In addition, therapeutic polypeptides may be used to treat autoimmune disorders such as multiple sclerosis; Sjogren's syndrome; sarcoidosis; insulin dependent diabetes mellitus; autoimmune thyroiditis; arthritis (e.g., osteoarthritis, rheumatoid arthritis, reactive arthritis, and psoriatic arthritis); ankylosing spondylitis; and scleroderma. Also, therapeutic polypeptides of the present invention can be used to treat acute and chronic inflammatory disorders, to promote increase in stature, to promote wound healing, and to prevent rejection after transplantation of cells, tissues, or organs.
In some preferred embodiments, the polypeptide is G-CSF. G-CSF induces rapid proliferation and release of neutrophilic granulocytes to the bloodstream, thereby providing a therapeutic effect in fighting infection. As explained in U.S. Pat. No. 6,831,158, recombinant human (rh)-G-CSF is generally used for treating various forms of leukopenia (a reduced level of white blood cells) and neutropenia (a reduced level of neutrophils). Leukopenia and neutropenia result in an increased susceptibility to various infections.
Commercial preparations of rh-G-CSF are available under the names filgrastim (GRAN® and NEUPOGEN®), lenograstim (NEUTROGIN® and GRANOCYTE®) and nartograstim (NEU-UP®). GRAN® and NEUPOGEN® are non-glycosylated and produced in recombinant E. coli cells. NEUTROGIN® and GRANOCYTE® are glycosylated and produced in recombinant CHO cells, NEU-UP® is non-glycosylated with five amino acids substituted at the N-terminal region of intact rh-G-CSF produced in recombinant E. coli cells.
Aside from G-CSF, per se, G-CSF analogs that are biologically functional or have biological activity are also useful. Methods of preparing rh-G-CSF are disclosed in U.S. Pat. No. 4,810,643. Various G-CSF analogs are also reported in U.S. Pat. No. 4,810,643. The polynucleotide encoding rh-G-CSF and the amino acid structure of rh-G-CSF are both provided in U.S. Pat. No. 5,985,265.
A representative example of an amino acid sequence (SEQ ID NO: 2450) (and the corresponding polynucleotide sequence (SEQ ID NO: 2451)) of a protein conjugate of the present invention is shown in Table 4. The PHO leader sequence is included.
In the amino acid sequence, the PHO leader sequence is from amino acids 1 to 18, G-CSF is from amino acids 19 to 192, and the NNT155 amino acid extension (NNT155 disclosed as SEQ ID NO: 2) is from amino acids 193 to 347. The stop codon is denoted by the “*” symbol.
As depicted in the polynucleotide sequence (SEQ ID NO: 2451), nucleic acids 1 to 54 encode the PHO leader sequence, nucleic acids 55 to 576 encode G-CSF, and nucleic acids 577 to 1041 encode the NNT155 amino acid extension (NNT155 disclosed as SEQ ID NO: 2). Nucleic acids 1042 to 1044 (TAG) constitute the stop codon.
In some embodiments, the number of repeating peptide units is between 75 and 225. Thus, in the case of a protein conjugate containing G-CSF linked to a polypeptide containing repeating units of peptide motif having the sequence NNT, embodiments of the present invention may include any of the following protein conjugates ((NNT)75-(NNT)225 disclosed as SEQ ID NOS: 4-83, 4748 and 84-153, respectively, in order of appearance): G-CSF-(NNT)75, G-CSF-(NNT)76, G-CSF-(NNT)77, G-CSF-(NNT)78, G-CSF-(NNT)79, G-CSF-(NNT)80, G-CSF-(NNT)81, G-CSF-(NNT)82, G-CSF-(NNT)83, G-CSF-(NNT)84, G-CSF-(NNT)85, G-CSF-(NNT)86, G-CSF-(NNT)87, G-CSF-(NNT)88, G-CSF-(NNT)89, G-CSF-(NNT)90, G-CSF-(NNT)91, G-CSF-(NNT)92, G-CSF-(NNT)93, G-CSF-(NNT)94, G-CSF-(NNT)95, G-CSF-(NNT)96, G-CSF-(NNT)97, G-CSF-(NNT)98, G-CSF-(NNT)99, G-CSF-(NNT)100, G-CSF-(NNT)101, G-CSF-(NNT)102, G-CSF-(NNT)103, G-CSF-(NNT)104, G-CSF-(NNT)105, G-CSF-(NNT)106, G-CSF-(NNT)107, G-CSF-(NNT)108, G-CSF-(NNT)109, G-CSF-(NNT)110, G-CSF-(NNT)111, G-CSF-(NNT)112, G-CSF-(NNT)113, G-CSF-(NNT)114, G-CSF-(NNT)115, G-CSF-(NNT)116, G-CSF-(NNT)117, G-CSF-(NNT)118, G-CSF-(NNT)119, G-CSF-(NNT)120, G-CSF-(NNT)121, G-CSF-(NNT)122, G-CSF-(NNT)123, G-CSF-(NNT)124, G-CSF-(NNT)125, G-CSF-(NNT)126, G-CSF-(NNT)127, G-CSF-(NTT)128, G-CSF-(NNT)129, G-CSF-(NNT)130, G-CSF-(NNT)131, G-CSF-(NNT)132, G-CSF-(NNT)133, G-CSF-(NNT)134, G-CSF-(NNT)135, G-CSF-(NNT)136, G-CSF-(NNT)137, G-CSF-(NNT)138, G-CSF-(NNT)139, G-CSF-(NNT)140, G-CSF-(NNT)141, G-CSF-(NNT)142, G-CSF-(NNT)143, G-CSF-(NNT)144, G-CSF-(NNT)145, G-CSF-(NNT)146, G-CSF-(NNT)147, G-CSF-(NNT)148, G-CSF-(NNT)149, G-CSF-(NNT)150, G-CSF-(NNT)151, G-CSF-(NNT)152, G-CSF-(NNT)153, G-CSF-(NNT)154, G-CSF-(NNT)155, G-CSF-(NNT)156, G-CSF-(NNT)157, G-CSF-(NNT)158, G-CSF-(NNT)159, G-CSF-(NNT)160, G-CSF-(NNT)161, G-CSF-(NNT)162, G-CSF-(NNT)163, G-CSF-(NNT)164, G-CSF-(NNT)165, G-CSF-(NNT)166, G-CSF-(NNT)167, G-CSF-(NNT)168, G-CSF-(NNT)169, G-CSF-(NNT)170, G-CSF-(NNT)171, G-CSF-(NNT)172, G-CSF-(NNT)173, G-CSF-(NNT)174, G-CSF-(NNT)175, G-CSF-(NNT)176, G-CSF-(NNT)177, G-CSF-(NNT)178, G-CSF-(NNT)179, G-CSF-(NNT)180, G-CSF-(NNT)181, G-CSF-(NNT)182, G-CSF-(NNT)183, G-CSF-(NNT)184, G-CSF-(NNT)185, G-CSF-(NNT)186, G-CSF-(NNT)187, G-CSF-(NNT)188, G-CSF-(NNT)189, G-CSF-(NNT)190, G-CSF-(NNT)191, G-CSF-(NNT)192, G-CSF-(NNT)193, G-CSF-(NNT)194, G-CSF-(NNT)195, G-CSF-(NNT)196, G-CSF-(NNT)197, G-CSF-(NNT)198, G-CSF-(NNT)199, G-CSF-(NNT)200, G-CSF-(NNT)201, G-CSF-(NNT)202, G-CSF-(NNT)203, G-CSF-(NNT)204, G-CSF-(NNT)205, G-CSF-(NNT)206, G-CSF-(NNT)207, G-CSF-(NNT)208, G-CSF-(NNT)209, G-CSF-(NNT)210, G-CSF-(NNT)211, G-CSF-(NNT)212, G-CSF-(NNT)213, G-CSF-(NNT)214, G-CSF-(NNT)215, G-CSF-(NNT)216, G-CSF-(NNT)217, G-CSF-(NNT)218, G-CSF-(NNT)219, G-CSF-(NNT)220, G-CSF-(NNT)221, G-CSF-(NNT)222, G-CSF-(NNT)223, G-CSF-(NNT)224 and G-CSF-(NNT)225.
In other preferred embodiments, the polypeptide is EPO. As explained in Krantz, Blood 77:419 (1991), naturally occurring EPO stimulates the division and differentiation of committed erythoid progenitors in the bone marrow and exerts its biological activity by binding to receptors and erythroid precursors. EPO has been manufactured biosynthetically using recombinant technology as the product of a cloned human EPO (hEPO) gene inserted into and expressed in Chinese hamster ovary (CHO) cells. See Egrie, et al., Immunobiol. 72:213-224 (1986). The primary structure (i.e., amino acid sequence) of the predominant, fully processed form of hEPO is illustrated in U.S. Pat. No. 6,583,272. In EPO, there are two disulfide bridges between Cys7-Cys161 and Cys29-Cys33. The molecular weight of the polypeptide chain of EPO without the sugar moieties is 18,236 DA. In the intact EPO molecule, approximately 40% of the molecular weight is accounted for by carbohydrate groups that glycosylate the protein at glycosylation sites on the protein. See Sasaki, et al., J. Biol. Chem. 262:12059 (1987).
Because hEPO is essential in red blood formation, the hormone is useful in the treatment of blood disorders characterized by low or defective red blood cell production. Clinically, EPO is used in the treatment of anemia in chronic renal failure (CRF) patients. See Eschbach, et al., NEJM 316:73-78 (1987); Eschbach, et al., Ann. Intern. Med. 111:992 (1989); Egrie, et al., Kidney Intl. 33:262 (1988); and Lim et al., Ann. Intern. Med. 110:108-114 (1989). EPO has also been used for the treatment of anemia in Acquired Immune Deficiency Syndrome (AIDS) and cancer patients undergoing chemotherapy. See R. P. Datum, et al., Erythropoietin In Clinical Applications—An International Perspective 301-324 (M. B. Garnick, ed., Marcel Dekker 1990).
Amino acid and corresponding nucleotide sequences of EPO, as well as other biologically active polypeptides useful in the present invention, are set forth in Table 5. Two other amino acid sequences of EPO are set forth in Table 6.
The protein conjugate may further comprise one or more affinity tags. Generally, an affinity tag is a polypeptide segment that facilitates isolation, purification or detection of the fusion protein containing the affinity tag. In principle, any peptide or protein for which an antibody or other specific binding agent is available can be used as an affinity tag. Representative affinity tags include a poly-histidine tract, protein A (Nilsson, et al., EMBO J. 4:1075, (1985); Nilsson, et al., Methods Enzymol. 198:3, (1991)), glutathione S transferase (Smith et al., Gene 67:31 (1988)), maltose binding protein (Kellerman et al., Methods Enzymol, 90:459-463 (1982); Guan, et al., Gene 67:21-30 (1987)), Glu-Glu affinity tag (Grussenmeyer, et al., Proc. Natl. Acad. Sci. USA 82:7952-4 (1985); see oNDEPHO-1R), substance P, FlagTM peptide (Hopp, et al., Biotechnology 6:1204-10 (1988)), streptavidin binding peptide, thioredoxin, ubiquitin, cellulose binding protein, T7 polymerase, or other antigenic epitope or binding domain. See, in general, Ford, et al., Protein Expression and Purification 2:95-107 (1991). DNAs encoding affinity tags are available from commercial suppliers (e.g., Pharmacia Biotech, Piscataway, N.J.; New England Biolabs, Beverly, Mass.; and Eastman Kodak, New Haven, Conn.).
As in the case of the amino acid extension, the affinity tag may be situated at the N-terminal, C-terminal, or both N-terminal and C-terminal with respect to the biologically active polypeptide sequence.
The present invention is also directed to a method of making the protein conjugates. The method involves culturing a cell transformed with a chimeric DNA molecule encoding the protein conjugate under conditions whereby the DNA is expressed, thereby producing the protein conjugate; and extracting an expression product of the chimeric DNA molecule from the cell or culture medium (or a milieu from the cell culture). In contrast to protein conjugates formed by chemical means, e.g., the commercial product NEULASTA (PEG-G-CSF, which is a covalent conjugate of recombinant methionyl human G-CSF and monomethionyl polyethylene glycol), the conjugation in the present invention is performed recombinantly as opposed to through physical or chemical means, resulting in the production of the biologically active protein and the polypeptide as components of a continuous protein. A linker, e.g., about 10-20 amino acids in length, may be used to join. the protein with the amino acid extension.
The chimeric DNA molecule includes a gene or polynucleotide fragment that encodes a protein portion and one or more gene fragments e.g., oligonucleotides that together encode the polypeptide or amino acid extension. Oligonucleotides encoding the peptide motifs contained in the amino acid extension (and which encode the peptide motifs specifically disclosed herein) are set forth in Table 7, (The one-letter symbols used in Table 7 are explained in Table 8.) The DNA molecules may further contain fragments that encode affinity tags, linkers, as well as 5′ and 3′ regulatory elements. The gene or polynucleotide that encodes a protein portion may be any gene or polynucleotide known to encode the desired protein or polypeptide of the protein portion. Such genes and polynucleotides, and the printers used to generate them, are protein or polypeptide specific and well known in the art. The ligated oligonucleotides encoding the polypeptide portion may be produced according to procedures set forth above and described in Example 1. The oligonucleotides may be of any length, but are preferably designed to avoid the use of repetitive DNA sequences that are known to inhibit transcription. For instance, ligated oligonucleotides containing combinations of two glutamate codons are less likely to adopt a structural configuration that impedes gene expression than a polynucleotide made up of only one glutamate codon. The chimeric DNA molecule encoding the protein conjugate of the present invention may be engineered to contain codons encoding methionine (M) and/or proline (P) amino acid at its 5′ end to facilitate expression.
The conjugates of the present invention are made via standard recombinant techniques in molecular biology, in some embodiments, a gene or polynucleotide encoding the biologically active protein is first cloned into a construct, e.g., a plasmid or other vector. Then, the oligonucleotides that encode the repeating units of the polypeptide portion are cloned into the construct through a ligation or multimetization scheme, in which the oligonucleotides are ligated together to form a polynucleotide that encodes the polypeptide portion. In this manner, the oligonucleotides are added to the gene or polynucleotide that encodes the protein portion, thereby producing the chimeric DNA molecule within the construct. As an option, the chimeric DNA molecule may be transferred or cloned into another construct that is a more appropriate expression vector. At this point, a host cell capable of expressing the chimeric DNA molecule is transformed with the chimeric DNA molecule. The transformation may occur with or without the utilization of a carrier, such as an expression vector. Then, the transformed host cell is cultured under conditions suitable for expression of the chimeric DNA molecule, resulting in the encoding of the protein conjugate.
Methods of ligation or multimerization useful in the present invention are well known. See, Joseph Sambrook, et al., Molecular Cloning: A Laboratory Manual, 2nd ed., 1.53 (Cold Spring Harbor Laboratory Press 1989).
The cloning process may take place through “directional cloning”, which is well known in the art. Directional cloning refers to the insertion of a polynucleotide into a plasmid or vector in a specific and predefined orientation. Once cloned into a vector, a polynucleotide sequence can be lengthened at its 3′ end or other polynucleotides inserted at its 5′ and/or 3′ ends. Such a design provides an efficient and relatively easy way to create large polymers without having to perform multiple rounds of ligation. The vector preferably contains restriction sites upstream of a cloned polynucleotide, but downstream of regulatory elements required for expression to facilitate the insertion of the second polynucleotide.
To facilitate directional cloning, “adapter oligonucleotides” may be ligated to the 5′ and 3′ ends of the chimeric DNA molecule encoding the protein conjugate. Preferably, the adapters contain restriction sites that are compatible with those present in the expression vector. The 3′ adapter oligonucleotide may also comprise a stop codon to designate the end of the encoding sequence to which it is ligated. The oligonucleotides encoding the polypeptide portion are preferably added in excess of the adapter oligonucleotides to increase the likelihood that a long polynucleotide is generated after ligation.
The methodology is not limited to any particular cloning strategy. The skilled artisan may use any variety of cloning strategies to produce a construct that comprises a chimeric DNA molecule of the present invention.
The chimeric DNA molecule can be introduced into the host cells in accordance with known techniques well known to those skilled in the art. These techniques include, but are not limited to, transformation using calcium phosphate co-precipitated chimeric DNA molecules, lipidic reagent co-transfection (i.e., LipofectamineTM), electroporation, transduction by contacting the cells with a virus, or microinjection of the chimeric DNA molecules into the cells. The host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Suitable prokaryotic hosts for transformation include E. coli, Bacillus subtilis, Salmonella typhimurium and various species within the genera Pseudomonas, Streptomyces, and Staphylococcus, although others may also be employed as a matter of choice.
A wide variety of host/expression vector combinations are employed in expressing the protein conjugates of the present invention. Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell dihydrofolate reductase or neomycin resistance for eukaryotic cell culture, or such as tetracycline or ampicillin resistance in E. coli, or the S. cerevisiae TRP1 gene), and a promoter derived from a highly-expressed gene to direct transcription of a downstream structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), A-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and in some embodiments, a leader sequence capable of directing secretion of translated protein conjugate. The vector will further comprise an origin of replication to ensure maintenance of the vector and to, if desirable, provide amplification within the host.
Useful expression vectors that can be used include, for example, segments of chromosomal, non-chromosomal and synthetic DNA sequences. Suitable vectors include, but are not limited to, derivatives of SV40 and pcDNA. and known bacterial plasmids such as col EI, pCR1, pBR322, pMal-C2, pET, pGEX as described by Smith, et al., Gene 67:31-40 (1988), pMB9 and derivatives thereof, plasmids such as RP4, phage DNAs such as the numerous derivatives of phage I such as NM989, as well as other phage DNA such as M13 and filamentous single stranded phage DNA; yeast plasmids such as the 2 micron plasmid or derivatives of the 2 m plasmid, as well as centomeric and integrative yeast shuttle vectors; vectors useful in eukaryotic cells such as vectors useful in insect or mammalian cells; vectors derived from combinations of plasmids and phage DNAs, such as plasmids that have been modified to employ phage DNA or the expression control sequences; and the like. The requirements are that the vectors are replicable and viable in the host cell of choice. Low- or high-copy number vectors may be used as desired.
For example in a baculovirus expression system, both non-fusion transfer vectors, such as, but not limited to pVL941 (BamHI cloning site, available from Summers, et al., Virology 84:390-402 (1978)), pVL1393 (BamHI, SmaI, XbaI, EcoRI, NotI, XmaIII, BglII and PstI cloning sites; Invitrogen), pVL1392 (BglII, PstI, NotI, XmaIII, EcoRI, XbalI, SmaI and BamHI cloning site; Summers, et al., Virology 84:390-402 (1978) and Invitrogen) and pBlueBacIII (BamHI, BglII, PstI, NcoI and HindIII cloning site, with blue/white recombinant screening, Invitrogen), and fusion transfer vectors such as, but not limited to, pAc700 (BamHI and KpnI cloning sites, in which the BamHI recognition site begins with the initiation codon; Summers, et al., Virology 84:390-402 (1978)), pAc701 and pAc70-2 (same as pAc700, with different reading frames), pAc360 (BamHI cloning site 36 base pairs downstream of a polyhedrin initiation codon; Invitrogen (1995)) and pBlueBacHisA, B, C (three different reading frames with BamHI, BglII, PstI, NcoI and HindIII cloning site, an N-terminal peptide for ProBondTM purification and blue/white recombinant screening of plaques; Invitrogen (220) can be used.
Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking nontranscribed sequences. DNA sequences derived from the SV40 splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements. Mammalian expression vectors contemplated for use in the invention include vectors with inducible promoters, such as the dihydrofolate reductase promoters, any expression vector with a DHFR expression cassette or a DHFR/methotrexate co-amplification vector such as pED (PstI, SalI, SbaI, Sinai and EcoRI cloning sites, with the vector expressing both the cloned gene and DHFR; Randal J. Kaufman, 1991, Randal J. Kaufman, Current Protocols in Molecular Biology, 16, 12 (1991)). Alternatively a glutamine synthetase/methionine sulfoximine co-amplification vector, such as pEE14 (HindIII, XbalI, SmaI, SbaI, EcoRI and BclI cloning sites in which the vector expresses glutamine synthetase and the cloned gene; Celltech). A vector that directs episomal expression under the control of the Epstein Barr Virus (EBV) or nuclear antigen (EBNA) can be used such as pREP4 (BamHI, SfiI, XhoI, NotI, NheI, HindIII, NheI, PvuII and KpnI cloning sites, constitutive RSV-LTR promoter, hygromycin selectable marker; Invitrogen), pCEP4 (BamHI, XhoI, NotI, NheI, HindIII, NheI, PvuII and KpnI cloning sites, constitutive hCMV immediate early gene promoter, hygromycin selectable marker; Invitrogen), pMEP4 (KpnI, PvuI, NheI, HindIII, NotI, XhoI, SfiI, BamHI cloning sites, inducible methallothionein IIa gene promoter, hygromycin selectable marker, Invitrogen), pREP8 (BamHI, XhoI, NotI, HindIII, NheI and KpnI cloning sites, RSV-LTR promoter, histidinol selectable marker; Invitrogen), pREP9 (KpnI, NheI, HindIII, NotI, XhoI, SfiI, BamHI cloning sites, RSV-LTR promoter, G418 selectable marker; Invitrogen), and pEBVHis (RSV-LTR promoter, hygromycin selectable marker, N-terminal peptide purifiable via ProBondTM resin and cleaved by enterokinase; Invitrogen).
Selectable mammalian expression vectors for use in the invention include, but are not limited to, pRc/CMV (HindIII, BstXI, NotI, SbaI and ApaI cloning sites, G418 selection, Invitrogen), pRc/RSV (HindII, SpeI, BstXI, NotI, XbaI cloning sites, G418 selection, Invitrogen) and the like. Vaccinia virus mammalian expression vectors (see, for example, Randall J. Kaufman, Current Protocols in Molecular Biology 1612 (Frederick M. Ausubel, et al., eds. Wiley 1991) that can be used in the present invention include, but are not limited to, pSC11 (SmaI cloning site, TK- and β-gal selection), pMJ601 (SalI, SmaI, AflI, NarI, BspMII, BamHI, ApaI, NheI, SacII, KpnI and HindIII cloning sites; TK- and β-gal selection), pTKgptF1S (EcoRI, PstI, SalII, AccI, HindII, SbaI, BamHI and Hpa cloning sites, TK or XPRT selection) and the like.
Yeast expression systems that can also be used in the present include, but are not limited to, the non-fusion pYES2 vector (XbaI, SphI, ShoI, NotI, GstXI, EcoRI, BstXI, BamHI, SacI, KpnI and HindIII cloning sites, Invitrogen), the fusion pYESHisA, B, C (XbalI, SphI, ShoI, NotI, BstXI, EcoRI, BamHI, SacI, KpnI and HindIII cloning sites, N-terminal peptide purified with ProBondTM resin and cleaved with enterokinase; Invitrogen), pRS vectors and the like.
One particularly preferred vector for use in the present invention is the plasmid pCE2. The pCE2 plasmid may be obtained by any method known in the art. One such method, which was utilized in Example 2.A., is described in Leung, et al., Proc. Natl. Acad. Sci. USA 92:4813-4817 (1995).
In a preferred embodiment, the chimeric DNA molecules can be inserted into an expression vector that already contains the necessary elements for the transcription and translation of the inserted chimeric DNA molecule.
In addition, the expression vector containing the chimeric DNA molecule may include drug selection markers. Such markers aid in cloning and in the selection or identification of vectors containing chimeric DNA molecules. For example, genes that confer resistance to neomycin, puromycin, hygromycin, dihydrofolate reductase (DHFR), guanine phosphoribosyl transferase (GPT), zeocin, and histidinol are useful selectable markers. Alternatively, enzymes such as herpes simplex virus thymidine kinase (tk) or chloramphenicol acetyltransferase (CAT) may be employed. Immunologic markers also can be employed. Any known selectable marker may be employed so long as it is capable of being expressed simultaneously with the nucleic acid encoding a gene product. Further examples of selectable markers are well known to one of skill in the art and include reporters such as enhanced green fluorescent protein (EGFP), beta-galactosidase (β-gal) or chloramphenicol acetyltransferase (CAT).
Consequently, mammalian and typically human cells, as well as bacterial, yeast, fungi, insect, nematode and plant cells can used in the present invention as host cells and may be transformed by the expression vector as defined herein. In some cellular hosts, such as mammalian cells, the cell containing the chimeric DNA molecule may be “isolated” in that it is removed from its original environment (e.g., the natural environment if it is naturally occurring). In other embodiments, such as plants, the cells do not have to be isolated in that the whole plant may be used rather than a culture of plant cells or parts.
Examples of suitable cells include, but are not limited to, VERO cells, HELA cells such as ATCC No. CCL2, CHO cell lines such as ATCC No. CCL61, COS cells such as COS-7 cells and ATCC No. CRL 1650 cells, W138, BHK, HepG2, 3T3 such as ATCC No. CRL6361, A549, PC12, K562 cells, 293 cells, Sf9 cells such as ATCC No. CRL1711 and Cv1 cells such as ATCC No. CCL70.
Other suitable cells that can be used in the present invention include, but are not limited to, prokaryotic host cells strains such as Escherichia coli, (e.g., strain DH5-α), Bacillus subtilis, Salmonella typhimurium, or strains of the genera of Pseudomonas, Streptomyces and Staphylococcus. Further suitable cells that can be used in the present invention include yeast cells such as those of Saccharomyces such as Saccharomyces cerevisiae. 
Host cells containing the polynucleotides of interest can be cultured in conventional nutrient media (e.g., Ham's nutrient mixture) modified as appropriate for activating promoters, selecting transformants or amplifying genes. The culture conditions, such as temperature, pH and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan. Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents, all of which are well known to those skilled in the art. Embodiments that involve cell lysis may entail use of a buffer that contains protease inhibitors that limit degradation after expression of the chimeric DNA molecule. Suitable protease inhibitors include leupeptin, pepstatin or aprotinin. The supernatant then may be precipitated. in successively increasing concentrations of saturated ammonium sulfate.
The protein conjugates product may be purified via one or more techniques. Typically, purification entails combinations of individual procedures such as gel filtration, affinity purification, salt fractionation, ion exchange chromatography, size exclusion chromatography, hydroxylapatite adsorption chromatography, hydrophobic interaction chromatography and gel electrophoresis. Protein refolding steps can be used, as necessary, in completing configuration of the protein conjugate. High performance liquid chromatography (HPLC) is often useful for final purification steps. See, in general, Robert K. Scopes, Protein Purification: Principles and Practice (Charles R. Castor, ed., Springer-Verlag 1994) and Joseph Sambrook, Molecular Cloning: A Laboratory Manual, 2nd edition (Cold Spring Harbor Laboratory Press 1989). Examples of multi-step purification separations are also described in Baron, et al., Crit. Rev. Biotechnol. 10:179-90 (1990) and Below, et al., J. Chromatogr. A. 679:67-83 (1994).
The conjugates are tested prior to use to determine whether they exhibit modified plasma half-life compared to the unconjugated protein. For example, in experiments conducted with G-CSF and various amino acid extensions such as (NNT), Applicants found that the half-life was increased in one case, and in other cases, was decreased. The tests may be conducted in accordance with standard techniques in pharmacokinetics, as shown in example 3. This procedure entails administration of a predetermined dose of the conjugate to an animal, preferably a laboratory animal such as a rodent, e.g., mouse, collect plasma from the animal at predetermined intervals, and analyze the plasma e.g., via Enzyme-Linked Immunosorbent Assay (“ELISA”), to determine concentration of the conjugate, until concentration was no longer measurable. The half-life may be calculated via a non compartmental pharmacokinetic analysis (e.g., using WINNonLin software version 4.1). In addition to the last time at which the conjugate concentration was measurable (tf), the analysis includes observation or calculation of the following main parameters: λz, apparent terminal rate constant associated to the apparent terminal phase, estimated by linear regression analysis of the logarithm of the plasma concentrations versus time in the monoexponential terminal part of the curve, t1/2,z, apparent terminal half-life, calculated according to the following equation: t1/2,z=ln(2)/λz; AUC, area under the plasma concentration-time curve from time zero to infinity; AUC/D, area under the plasma concentration-time curve per unit of dose; MRT, mean residence time calculated as the ratio between the area under the first moment curve, AUMC, and AUC; CL, systemic clearance, calculated as CL=D/AUC; and Vss, steady state volume of distribution, calculated as Vss=CL*MRT.
A further aspect of the present invention relates to a composition comprising the protein conjugate and a carrier. Broadly, the carrier may be a culture medium or a matrix (e.g., a purification matrix). In some embodiments, the carrier is a pharmaceutically acceptable carrier, in which case the composition is useful for preventing or treating disorders and/or diseases in a human or animal, most preferably in a mammal, or for diagnostic purposes. As an active ingredient of the composition, the protein conjugate is preferably in a soluble form.
Generally, the composition comprises a pharmaceutically effective amount of the protein conjugate which achieves the desired effect e.g., therapeutic or diagnostic. Pharmaceutically effective amounts can be estimated from cell culture assays. For example, a dose can be formulated in animal models to achieve a circulating concentration range that includes or encompasses a concentration point or range having the desired effect in an in vitro system. See, e.g., Molineux, et al., Exp. Hematol. 27:1724-34 (1999). This information can thus be used to accurately determine the doses in other mammals, including humans and animals. In general, dosage amounts range from about 1 ng/kg to about 10 mg/kg based on weight of the subject.
Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or in experimental animals. See, e.g., Molineux, et al., Exp. Hematol. 27:1724-34 (1999). For example, the LD50 (the dose lethal to 50% of the population) as well as the ED50 (the dose therapeutically effective in 50% of the population) can be determined using methods known in the art. The dose ratio between toxic and therapeutic effects is the therapeutic index that can be expressed as the ratio between LD50 and ED50 compounds that exhibit high therapeutic indices.
The data obtained from the cell culture and animal studies can be used in formulating a range of dosage of such compounds which lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity.
The compositions can be administered via any suitable route such as locally, orally, systemically, intravenously, intramuscularly, mucosally, transdermally (e.g., via a patch). They may be encapsulated in liposomes, microparticles, microcapsules, nanoparticles and the like. Techniques for formulating and administering biologically active polypeptides are also disclosed in Remington: The Science and Practice of Pharmacy (Alfonso R. German), et al., eds. Philadelphia College of Pharmacy and Science 2000).
In order to fully illustrate the present invention and advantages thereof, the following specific examples are given, it being understood that the same are intended only as illustrative and in no way limitative.
Example 1
Cloning of Chimeric DNA Molecule
For ease of downstream protein purification, it was decided that the G-CSF-polymer proteins were secreted into the cell culture medium. Prior experience using bacterial (ST2) secretion signals with various cytokine-polymer constructs showed low secretion efficiency in both prokaryotic and eukaryotic systems. However, the use of the Schizosaccharomycen pombe secretion signal sequence of the pho1+ acid phosphatase (PHO) for the secretion of heterologous proteins (GIFT and HPV 16 E7) into a medium was known. Therefore, this secretion signal was tested with the G-CSF-polymer constructs described below in a CHO cell expression system. Also described below are the vectors that were synthesized for the production of G-CSF-polymer constructs and expression of G-CSF-polymers.
1A. Production of PHO×pBSK Construct
PRO×pBSK Construct
The first construct synthesized was simply the PRO leader sequence cloned into the bacterial cloning vector pBSK. The amino acid sequence of the PHO secretion signal is listed below,







(SEQ ID NO: 154)









M F L Q N L F L G F L A V V C A N A






The PHO secretion signal was synthesized by fusing two sets of complementary DNA oligonucleotides together and cloning them into pBSK. The most important consideration that went into the design of the oligonucleotides was that the fusion of the leader sequence to the N-terminus of the G-CSF-polymer be direct, without any intervening sequence. This ensured that the entire secretion signal was clipped from the molecule during processing, resulting in a secreted form of G-CSF with no amino-terminal modification when compared to naturally occurring and clinically available versions of G-CSF. By preparing the constructs in this manner, not only could direct comparisons to G-CSF and PEG-G-CSF be made, but this also limited any potential immunogenicity by introducing additional amino acids into the recombinant G-CSF protein. By incorporating restriction sites into the oligonucleotides for cloning the PHO leader into pBSK, as well as the subsequent cloning G-CSF into PHO×pBSK, these requirements were satisfied. The oligonucleotides that were used are listed below.









oNDEPHO-1F:







(SEQ ID NO: 155)









5′-GGCCGCCATATGTTCTTGCAAAATTTATTCCTTGGCT-3′



 



oNDEPHO-1R:







(SEQ ID NO: 156)









5′-CCAAAAAGCCAAGGAATAAATTTTGCAAGAACATATGGC-3′



 



oNDEPHO-2F:







(SEQ ID NO: 157)









5′-TTTTGGCCGTTGTTTGCGCAAACGCGTCCCGCAGGTG-3′



 



oNDEPHO-2R:







(SEQ ID NO: 158)









5′-GATCCACCTGCGGGACGCGTTTGCGCAAACAACGG-3′






A diagram of the PHO×pBSK vector is shown in FIG. 1. The PRO leader (PhoA) was cloned into pBSK using NotI and BamHI. The sequence for mature G-CSF was cloned into this construct utilizing the BspMI and BamHI sites. This vector confers ampicillin resistance (bla) when grown in bacteria.
Method of Construction
Complementary pairs of oligonucleotides (oNDEPHO-1F and oNDEPHO-1R) and (oNDEPHO-2F and oNDEPHO-2R) were phosphorylated using T4 Polynucleotide Kinase (PNK). The T4 PNK was heat-inactivated and the oligonucleotide pairs were allowed to slowly anneal on ice. The reactions were diluted in TE and used in a ligation with pBSK. previously digested using NotI and BamHI. Ligation products were electroporated into Top10 competent cells and grown on LB-ampicillin plates. Minipreps were performed on ampicillin resistant colonies to isolate DNA and diagnostic digests identified putative clones. Sequence analysis determined which of the putative clones were correct.
1.B. Production of PRO-G-CSF-NN×pBSK Construct
PHO-G-CSF-NN×pBSK Construct
This construct resulted from the cloning of PCR amplified material corresponding to the coding sequence of mature G-CSF into the PHO×pBSK vector using BspMI and BamHI. As stated previously, the oligonucleotides used for this purpose were designed to ensure that the junction between PRO and G-CSF had no intervening sequence by utilizing the restriction enzyme BspMI. Furthermore, the C-terminus of G-CSF had a direct fusion of two asparagine residues (NN) and restriction sites for the enzymes BbsI and BamHI. BbsI was subsequently utilized to directly add the NNT polymer to the C-terminus of G-CSF, while BamHI was used to clone GCSF-NN into the vector.
The oligonucleotides that were synthesized to amplify G-CSF are as follows:







oBspMIGCSF:







(SEQ ID NO: 159)







5′-CGATCGACCTGCAAGTCGCGACTCCGCTGGGTCCAGCTA-3′


 


oGCSFBbsBam:







(SEQ ID NO: 160)







5′-CGGGATCCGAAGACGTGTTGTTAGGCTGGGCAAGGTGGC-3′ 3′






A diagram of the PHO-G-CSF-NN×pBSK vector is shown in FIG. 2. The sequence for mature G-CSF-NN was cloned into PHO×pBSK using BspMI (destroyed) and BamHI. The subsequent addition of an NNT polymer utilized the BbsI and BamHI sites indicated on the plasmid map. This vector confers ampicillin resistance (bla) when grown in bacteria.
Method of Construction
G-CSF was amplified by PCR using oBspMIGCSF and oGCSFBbsBam oligonucleotides. The ≈520 bp band corresponding to mature G-CSF was excised from an agarose gel and purified. The purified fragment was digested with BspMI and BamHI, purified and ligated into PHO×pBSK cut with the same enzymes. The ligation products were electroporated into Top10 competent cells and grown on LB-ampicillin plates. Minipreps were performed on ampicillin resistant colonies to isolate DNA and diagnostic digests identified putative clones. Sequence analysis determined which of the putative clones were correct.
1.C. Production of PHO-G-CSF-NNT65×pBSK Construct (NNT65 Disclosed as SEQ ID NO: 1)
PHO-G-CSF-NNT65×pBSK Construct (NNT65 Disclosed as SEQ ID NO: 1)
The amino acid composition of this polymer encodes for the consensus mammalian N-linked glycosylation site, N-X-(S/T). Therefore, the polymer may be glycosylated on the threonine residues of the polymer extension when this construct is expressed in CHO cells. The expectation was that the polymeric increase in translated product size and posttranslational modification would modulate the pK parameters of G-CSF, conferring upon the protein-enhanced half-life in serum without decreasing its biological activity.
The construction of this polymer was achieved using an oligonucleotide ligation/multimerization scheme. By cutting the PHO-G-CSF-NN×pBSK construct with BbsI, a four base underhang (GTTG) was created in the two asparagines residues added to the C-terminus of G-CSF. By designing complementary sets of oligonucleotides that code for repeating NNT triplets as well as anneal to the GTTG underhang, it was possible to multimerize the oligonucleotides that code for 9 amino acids into longer chains. Short adaptors containing a stop codon, a BbsI site for future extension of the polymer and a BamHI site were added in low ratios to terminate the multimerization and allow for coning of the BbsI-BamHI polymer fragment into PHO-G-CSF-NN×pBSK.
The oligonucleotides used to synthesize the NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1) are listed below:
Polymer Backbone Oligonucleotides









o3NNTF:







(SEQ ID NO: 161)









5′-CAACACCAACAATACCAACAATACAAA-3′


 



o3NNTR:







(SEQ ID NO: 162)









5′-GTTGTTTGTATTGTTGGTATTGTTGGT-3′






Adaptor Oligonucleotides










oDent3F:







(SEQ ID NO: 163)









5′-CAACTAGTCTTCG-3′


 



oDent3R:







(SEQ ID NO: 164)









5′-GATCCGAAGACTA-3′






The following sequence (NTNNTNNTN) (SEQ ID NO: 165) was the repeating unit of the NNT polymer that was produced using the polymer backbone oligonucleotides of o3NNTF and o3NNTR, which show a CAAC overhang and GTTG underhang respectively that were used to multimerize the polymer.







(SEQ ID NO: 165)









     N   T   N   N   T   N   N   T   N


 







(o3NNTF)(SEQ ID NO: 166)









5′-C AAC ACC AAC AAT ACC AAC AAT ACA AA-3′


 







(o3NNTR)(SEQ ID NO: 167)









3′-TGG TTG TTA TGG TTG TTA TGT TTG TTG-5′






The following is the terminating adaptor molecule that completed the polymer and included a stop codon, BbsI site for future extension of the polymer and a BamHI site that is necessary for cloning.
Terminating Adaptor Molecule









     N   *







(oDent3F)(SEQ ID NO: 168)









5′-C AAC TAG TCT TCG-3′


 







(oDent3R)(SEQ ID NO: 169)









3′-ATC AGA AGC CTA G-5′



BbsI BamHI






BbsI BamHI
A diagram of the PHO-G-CSF-NNT65×pBSK vector (NNT65 disclosed as SEQ ID NO: 1) is shown in FIG. 3. The addition of NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1) utilized the BbsI site (destroyed) that was located at the C-terminus of G-CSF and BamHI. As shown in FIG. 3, the BbsI site was regenerated at the end of the NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1) for future extension of length. This vector confers ampicillin resistance (bla) when grown in bacteria.
Method of Construction
Complementary pairs of polymer backbone oligonucleotides (o3NNTF and o3NNTR) and adaptor oligonucleotides (oDent3F and oDent3R) were phosphorylated using T4 PNK. The T4 PNK was heat-inactivated and the oligonucleotide pairs were allowed to slowly anneal on ice. Polymer multimerization was performed by mixing polymer and adaptor duplexes at 20:1 and 40:1 ratios with T4 Ligase. The T4 ligase was heat-inactivated and the entire ligation reactions were digested with BamHI overnight. Both reactions were precipitated and ran on an acrylamide gel. Material between 250 bp-800 bp was excised and gel purified.
This material was used in a ligation with PHO-G-CSF-NN×pBSK that had been digested with BbsI and BamHI Chemically competent Stb12 cells were transformed with the ligation products and grown on LB-ampicillin plates. Minipreps were performed to isolate DNA and diagnostic digests identified putative Clones. Sequence analysis determined which of the putative clones were correct.
The longest clone isolated from this strategy was PHO-G-CSF-NNT65×pBSK (NNT65 disclosed as SEQ ID NO: 1).
1.D. Production of PHO-G-CSF-NNT155×pBSK Construct (NNT155 Disclosed as SEQ ID NO: 2)
PHO-G-CSF-NNT155×pBSK Construct (NNT155 Disclosed as SEQ ID NO: 2)
The construction of this clone required the addition of additional NNT residues to the PHO-G-CSF-NNT65×pBSK construct (NNT65 disclosed as SEQ ID NO: 1) using the same oligomerization scheme. The nucleotide composition of the oligonucleotides used in this extension was altered to identify the junction between the original polymer and the extension. These alterations maintained the original NNT composition of the polymer and utilized the same GTTG underhang and CAAC overhang strategy. By digesting PHO-GCSF-NNT65 (NNT65 disclosed as SEQ ID NO: 1) with BbsI and BamHI, it was possible to extend the length of the polymer using the same oligonucleotide multimerization strategy as before.
The oligonucleotides used to extend the NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1) to NNT155 (NNT155 disclosed as SEQ ID NO: 2) are listed below:
Polymer Backbone Oligonucleotides









o3NNTextF:







(SEQ ID NO: 170)









5′-CAACACCAATAATACCAACAATACAAA-3′


 



o3NNTextR:







(SEQ ID NO: 171)









5′-GTTGTTTGTATTGTTGGTATTATTGGT-3′






Adaptor Oligonucleotides










oDent3F:







(SEQ ID NO: 172)









5′-CAACTAGTCTTCG-3′


 



oDent3R:







(SEQ ID NO: 173)









5′-GATCCGAAGACTA-3′






As with the production of the PHO-G-CSF-NNT65×pBSK Construct (NNT65 disclosed as SEQ ID NO: 1), NTNNTNNTN (SEQ ID NO: 165) was the repeating unit of the NNT polymer extension that was produced using the polymer backbone oligonucleotides of o3NNTextF and o3NNTextR, in which the CAAC overhang and GTTG underhang were still used to multimerize the polymer and the amino acid composition was unchanged from the original NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1).







(SEQ ID NO: 165)









     N   T   N   N   T   N   N   T   N


 







(o3NNTextF)(SEQ ID NO: 174)









5′-C AAC ACC AAT AAT ACC AAC AAT ACA AA-3′


 







(o3NNTextR)(SEQ ID NO: 175)









3′-TGG TTA TTA TGG TTG TTA TGT TTG TTG-5′






The above underlined nucleotides of o3NNTextF and o3NNTextR differed from the nucleotides in the same position in o3NNTF and o3NNTR respectively.
The following is the terminating adaptor molecule that completed the NNT155 polymer (NNT155 disclosed as SEQ ID NO: 2) and included the BamHI site necessary for cloning. oDent3F and oDent3R are the same oligonucleotides that were used for the initial NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1).
Terminating Adaptor Molecule









     N   *







(oDent3F)(SEQ ID NO: 176)









5′-C AAC TAG TCT TCG-3′


 







(oDent3R)(SEQ ID NO: 177)









3′-ATC AGA AGC CTA G-5′



       BbsI BamHI






BbsI BamHI
A diagram of the PHO-G-CSF-NNT155×pBSK vector (NNT155 disclosed as SEQ ID NO: 2) is shown in FIG. 4. The extension of the NNT65 polymer (NNT65 disclosed as SEQ ID NO: 1) by 90AA utilized the BbsI site (destroyed) that was located at the C-terminus of PHO-G-CSF-NNT65×pBSK (NNT65 disclosed as SEQ ID NO: 1) and BamHI. It was noted that the BbsI site was regenerated at the end of the NNT155 (NNT155 disclosed as SEQ ID NO: 2) polymer for future extension of length. This vector confers ampicillin resistance (bla) when grown in bacteria.
Method of Construction
Complementary pairs of polymer backbone oligonucleotides o3NNTextF and o3NNTextR, and adaptor oligonucleotides oDent3F and oDent3R were phosphorylated using T4 PNK. The T4 PNK was heat-inactivated and the oligonucleotide pairs were allowed to slowly anneal on ice. Polymer oligomerization was performed by mixing polymer and adaptor duplexes at 20:1 and 40:1 ratios with T4 Ligase. The T4 Ligase was heat-inactivated and the entire ligation reactions were digested with BamHI overnight. Both reactions were precipitated and ran on an acrylamide gel. Material between 250 bp to 800 bp was excised and gel purified. This material ligated into PHO-G-CSF-NNT65×pBSK (NNT65 disclosed as SEQ ID NO: 1) digested with BbsI and BamHI. Chemically competent Stb12 cells were transformed with the ligation products and grown on LB-ampicillin plates. Minipreps were performed to isolate DNA and diagnostic digests identified putative clones. Sequence analysis determined which of the putative clones were correct.
The longest clone isolated from this strategy was PHO-G-CSF-NNT155×pBSK (NNT155 disclosed as SEQ ID NO: 2).
Example 2
Transformation of Host Cell and Expression of Chimeric DNA Molecule
2.A. Production of PHO-G-CSF-NNT155×pCE2 Construct (NNT155 Disclosed as SEQ ID NO: 2)
Preparation of Vector pCE2
The plasmid pCE2 was derived from the plasmid pREP7b, through the following manipulations. First, the 2000 bp EBNA coding region was deleted. Next, pBR322ori was replaced with pKS-ori. Then, the RSV promoter region was replaced by the CMV enhancer and the elongation factor-1a (EF-1a) promoter and intron.
The CMV enhancer was derived from a 380 bp XbaI-SphI fragment produced by the polymerase chain reaction (PCR) from pCEP4 (Invitrogen, San Diego, Calif.) using the following primers:







(SEQ ID NO: 178)









5′-GGCTCTAGATATTAATAGTAATCAATTAC-3′;



and


 







(SEQ ID NO: 179)









5′-CCTCACGCATGCACCATGGTAATAGC-3′.






The EF-1a promoter and intron (Uetsuki, et al., J. Biol. Chem. 264:5791-5798 (1989)) were derived from a 1200 bp SphI-Asp718I fragment produced by PCR from human genomic DNA using the following primers:







(SEQ ID NO: 180)









5′-GGTGCATGCGTGAGGCTCCGGTGC-3′;



and


 







(SEQ ID NO: 181)









5′-GTAGTTTTCACGGTACCTGAAATGGAAG-3′.






The two fragments were ligated into a XbaI/Asp718I digested vector derived from pREP7b to generate pCE2.
PHO-G-CSF-NNT155×pCE2 Construct (NNT155 Disclosed as SEQ ID NO: 2)
In order to express PHO-G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) in mammalian cells, it was necessary to move the construct into the vector pCE2. This vector contained the minimal promoter and the first intron for the human elongation factor-1-α flanked by the immediate-early CMV enhancer. The vector also contained the hygromycin B resistance marker for mammalian selection.
A diagram of the PHO-G-CSF-NNT155×pCE2 vector (NNT155 disclosed as SEQ ID NO: 2) is shown in FIG. 5. The promoter that drives expression in CHO cells is Pcmv/ef-1a. The vector was linearized for electroporation into CHO cells using SalI. This vector confers resistance to hygromycin B in mammalian cells and ampicillin resistance (bla) when grown in bacteria.
Method of Construction
This construct was produced by isolating and gel purifying the 1100 bp NotI-BamHI fragment from PHO-G-CSF-NNT155×pBSK (NNT155 disclosed as SEQ ID NO: 2). This material was ligated into pCE2 that had been digested with NotI and BamHI. Chemically competent Stb12 cells were transformed with the ligation products and grown on LB-ampicillin plates. Minipreps were performed to isolate DNA and diagnostic digests identified putative clones. Large-scale maxipreps were performed to isolate microgram quantities of the plasmid for CHO cell transformation.
2.B. Production of Transfectant Cell Lines
In order to produce the polymers described above, mammalian cells were used as host cells for expression. In this instance, Chinese hamster ovary (CHO) cell lines were chosen. CHO cells are widely used in the pharmaceutical industry to express recombinant protein therapeutics including G-CSF and EPO. As described below, expression cultures of G-CSF-polymer constructs in CHO cells were established.
Establishment of Adherent Cultures
The PHO-G-CSF-NNT155×pCE2 vector (NNT155 disclosed as SEQ ID NO: 2) was linearized using the enzyme Sari. The digest was precipitated and re-suspended in 50 μL of TE. One (1) μg of this plasmid was used in an electroporation along with 5×106 CHO cells. Adherent CHO cells were grown in Ham's Nutrient Mixture F-12 (F-12 Ham's media) containing 10% FBS. The cells were allowed to recover overnight, and the next day media containing 700 μg/mL of hygromycin B was added to begin selection of resistant cells. The media was changed every 2-3 days as needed over the course of 2-3 weeks. Bulk pools of resistant cells were isolated and passaged two additional times in the presence of hygromycin B.
To test these cells for the secretion of PHO-G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) into the media, the cells were grown in Ham's media containing low serum media (0.5%) for 3-5 days. The media was isolated and used in Western blots that were probed using a polyclonal antibody against G-CSF. The blots are reproduced in FIGS. 6 and 7. The difference between the blots is that the samples in FIG. 7 were additionally subjected to Peptide:N Glycosidase F (PNGase F) treatment. As shown in FIG. 6, the blots showed immunoreactive material migrating at apparent molecular weight≈95 kDa. As shown in FIG. 7, digestion of these same samples with PNGase F, a glycosidase that removes N-linked glycosylation chains, reduced the immunoreactive material to apparent molecular weight≈49 kDa. This corresponded approximately to the theoretical size of unmodified G-CSF-NNT155 protein (NNT155 disclosed as SEQ ID NO; 2). Native G-CSF migrates electrophoretically at ≈18 kDa; the addition of the NNT polymer to the C-terminus adds substantial mass to the recombinant, polymeric molecule. The expression also appeared quite stable; no appreciable proteolytic degradation was observed for the unpurified protein present in conditioned medium. Further, as shown in FIG. 7, the decrease in size of the constructs after PNGase F treatment suggested the recombinant protein constructs were subject to a substantial amount of glycosylation.
Establishment of Suspension Cultures
To facilitate purification of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) found in the conditioned media of established CHO cultures, cells were grown in a chemically defined, low protein, serum-free media (PROCHO4-CDM, Cambrex). In the process of adapting the cells to this media, the cells adapted from adherent to suspension growth.
Cells were grown in F-12 Ham's+10% FBS to near confluency in T-185 flasks, trypsinized and suspended in PROCHO4-CDM media. 107 cells were added to 50 mL of PROCHO4-CDM and incubated in T-185 flasks. After 4-5 passages, approximately 90% of the cells were no longer adherent and grew as a mixture of single cell and aggregated cell clumps. For conditioned media collections, typically 60 mL of fresh PROCHO4-CDM media was incubated with 7-8 ml, of a high cell density culture for 5-6 days. Cells were removed from the media by centrifugation and the media was subsequently clarified using a 0.2 micron. filter. The media was quantitated for yield of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) by Western blot (typically 100-200 μg/L) and stored until needed.
2.C. Expression of G-CSF-NNT Constructs in PROCHO4-CDM
Samples were conditioned media from the foregoing bulk CHO cell lines grown for 6 days in PROCHO4-CDM. Western blots were probed using polyclonal antibody against G-CSF. As shown in FIG. 8, the size of both constructs were the same as was seen in Ham's media (as described above) and there was no degradation observed in the G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) cell lines.
2.D. Optimization of Expression
Various chemical and nutrient additives as well as various environmental parameters were tested in an attempt to determine growth conditions necessary to maximize expression of the desired product. The following approaches resulted in an increase in protein accumulation.
Chemical Additives
Although it was known that not all chemical additives result in an increase in protein production, published literature indicated that the addition of adenosine or AMP to 2.5 mM leads to cell cycle arrest; effectively prolonging cell culture viability with a concomitant increase in protein accumulation. The effect of AMP was tested on CHO-mediated production of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) production in ProCHO4 chemically defined medium (CDM). AMP was added at a final concentration of 1 mM in ProCHO4 CDM. No decrease in cell viability compared to control was observed. The addition of AMP resulted in a slight increase in protein production,
Environmental Parameters
Temperature Changes
Reduced incubation temperatures for CHO cultures can lead to markedly enhanced levels of protein production. As was found with other protein production enhancement methods, the observed effect is due to enhanced protein production during cell cycle arrest. The effect of reducing the incubation temperature of the recombinant CHO line from 37° C. to 28° C. was examined. Although cultures maintained at 28° C. remained viable considerably longer than those at 37° C., the lower temperature did not result in higher recombinant protein production.
Adaptation to Suspension Culture
The bulk CHO population was converted to spinner flask culture conditions. Adaptation to suspension culture was mediated by growth in ProCHO4 CDM. Following adaptation, cells were expanded in T-flasks and seeded into spinner flasks containing ProCHO5 CDM at various densities. A marked increase in protein production was observed. during adaptation to suspension culture in ProCHO5 CDM, regardless of Whether the cells were grown in static or spinner cultures.
Use of Different Cell Lines as Hosts
One approach to optimization of expression may be to use a new cell line for host cells. Accordingly, a new shipment of CHO-K1 from ATCC was obtained. The new population was propagated and banked at an early passage for future use. This defined culture was used to generate stable clonal cell lines expressing the recombinant protein of interest. Briefly, CHO-K1 cells were electroporated with the vector of interest and selected for stable expression of hygromycin. 92 colonies were isolated and evaluated for expression of the recombinant protein of interest. Many of these colonies exhibited expression levels that were markedly higher than that of the original transfected population, described above.
Results
A very slight enhancement of expression was observed when cultures were treated with 1 mM AMP. Reduced culture temperatures increased the longevity of the cultures, but there was no enhancement of protein expression. Adaptation to suspension culture conditions in ProCHO5 CDM dramatically enhanced expression of the recombinant protein. Also, isolated clones from an ATCC-defined CHO-K1 cell line expressed the desired protein at significantly higher levels than the originally isolated population.
Example 3
Pharmacokinetic Evaluation of G-CSF-NNT155 Conjugate (NNT155 Disclosed as SEQ ID NO: 2)
The pharmacokinetic parameters of the G-CSF-NNT155 protein conjugate (NNT155 disclosed as SEQ ID NO: 2) was evaluated. Three other compounds were included as positive controls. The controls were NEULASTA (PEG-G-CSF), NEUPOGEN (rh-G-CSF) and G-CSF compounds. The compounds were tested by single intravenous (i.v.) administration to mice and blood was collected up to 72 hours post-dosing. The plasma was analyzed by the ELISA method.
3.A. Analytical Method
The assay employed the quantitative sandwich enzyme immunoassay technique. A monoclonal antibody specific for G-CSF had been pre-coated onto a microplate. Standards and samples were pipetted into the wells. Any G-CSF present was bound by the immobilized antibody. After washing away any unbound substances, an enzyme-linked polyclonal antibody specific for G-CSF was added to the wells. Following a wash to remove any unbound antibody-enzyme reagent, a substrate solution was added to the wells and color developed in proportion to the amount of G-CSF bound in the initial step. The color development was stopped and the intensity of the color was measured.
Reagents
The following reagents and material were used:

    
    
        G-CSF Microplate: 96 well polystyrene microplate (12 strips of 8 wells) coated with a murine monoclonal antibody against G-CSF.
        G-CSF conjugate: 21 mL of polyclonal antibody against G-CSF conjugated to horseradish peroxidase, with preservative.
        G-CSF standard: 2 vials (25 ng/mL) of recombinant human G-CSF in a buffered protein base with preservative, lyophilized.
        Assay Diluent RD1A: 11 mL of a buffered protein base with preservative.
        Calibrator Diluent RD5: 21 mL of a buffered protein base with preservative. For cell culture supernate samples.
        Calibrator Diluent RD6A: 21 mL of animal serum with preservative. For serum/plasma samples.
        Wash Buffer Concentrate: 21 mL of a 25-fold concentrated solution of buffered surfactant with preservative.
        Color Reagent A: 12.5 mL of stabilized hydrogen peroxide,
        Color Reagent B: 12.5 mL of stabilized chromogen (tetramethylbenzidine).
        Stop Solution: 6 mL of 2N sulfuric acid.
        Plate Covers: 4 adhesive strips.

Reagent Preparation

    
    


20 mL of Wash Buffer Concentrate was diluted into deionized or distilled water to prepare 500 mL of Wash Buffer. The G-CSF Standard was reconstituted with 1 mL deionized or distilled water. This reconstitution produced a stock solution of 25000 pg/mL. The G-CSF standard was allowed to sit for a minimum of 15 minutes with gentle agitation prior to making dilutions. Nine hundred (900) μL of Calibrator Diluent RD6A was pipetted into a 2500 pg/mL tube. 600 μL of the same diluent was pipetted into the remaining 4 tubes. The stock solution was used to produce a dilution series: 25000 pg/mL (1:10)→2500 pg/mL and 25000 pg/mL (1:3)→833.3 pg/mL (1:3)→277.8 pg/mL (1:3)→92.6 pg/mL (1:3)→30.9 pg/mL. Each tube was mixed thoroughly before the next transfer. The 2500 pg/mL standard served as the high standard. The Calibrator Diluent RD6A served as the zero standard (0 pg/mL). The standard curve was performed with 6 point: 2500-833.3-277.8-92.6-30.9-0 pg/mL, double well for each point. For the substrate solution, Color Reagent A and B was mixed together in equal volumes within 15 minutes of use. The reagents were protected from light.
Assay Procedure
All reagents and samples were brought to room temperature before use. All reagents and working standards were prepared. One hundred (100) μL of Assay Diluent RD1A were added to each well, 100 μL of standard and an appropriate volume of sample were also added to each well. The wells were covered with an adhesive strip and incubated. for 2 h at room temperature. Each well was aspirated and washed with 400 μL of wash buffer, which was repeated twice for a total of three washes. After the last wash, any remaining wash buffer was removed by aspirating or decanting. The plate was inverted and blotted against clean paper towels. 200 μL of G-CSF conjugate was added to each well. The wells were covered with a new adhesive strip. The wells were incubated for 2 h at room temperature. The aspiration/wash described above was repeated. Two hundred (200) μL of Substrate Solution was added to each well. The wells were incubated for 20 min. at room temperature. The wells were protected from fight. Then, 50 μL of stop solution were added to each well. Finally, the optical density of each well within 30 min, was determined using a microplate reader (VersaMax-Molecular Device) set to 450 nm with correction to 570 nm (OD 450 nm-OD 570 nm).
Pharmacokinetic Analysis
A non-compartmental pharmacokinetic analysis (WINNonLin software version 4.1) was applied. The following main parameters were observed or calculated for each G-CSF construct: tf, last time at which each compound concentration was measurable; λz, apparent terminal rate constant associated to the apparent terminal phase, estimated by linear regression analysis of the logarithm of the plasma concentrations versus time in the mono-exponential terminal part of the curve; t1/2,z, apparent terminal half-life, calculated according to the following equation: t1/2,z=ln(2)/λz; AUC, area under the plasma concentration-time curve from time zero to infinity; AUC/D, area under the plasma concentration-time curve per unit of dose; MRT, mean residence time calculated as the ratio between the area under the first moment curve, AUMC, and AUC; CL, systemic clearance, calculated as CL=D/AUC; and Vss, steady state volume of distribution, calculated as Vss=CL*MRT,
Results
As shown in Table 9, pharmacokinetic studies in mice showed that G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) possessed a longer half-life (6.2 h) than either the G-CSF Control (1.53 h), NEUPOGEN compound (1.13 h) or the NEULASTA compound (3.04 h). G-CSF-NNT155's (NNT155 disclosed as SEQ ID NO: 2) longer half-life corresponded to a more sustained duration of effect compared to all three controls. A corresponding substantial decrease of systemic clearance was Observed for G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), accounting for the 9.5 mL/h/kg systemic clearance. Other conjugates containing amino acid extensions disclosed herein exhibited a decreased half-life relative to control.
Example 4
Bioavailability and Efficacy of G-CSF-NNT155 Conjugate (NNT155 Disclosed as SEQ ID NO: 2)
Neutropenia, a low absolute count of neutrophils, is a serious condition that can impede the fight against infections. To stimulate a peripheral increase in neutrophil counts, granulocyte colony stimulating factor (G-CSF) may be used as a therapy for neutropenia or in combination with other stimulating factors in collection of cells for transplant. The bioavailability of partially purified G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), PEG-G-CSF (NEULASTA) and rh-G-CSF (NEUPOGEN) was determined and compared via i.v. (intravenous) and s.c. (subcutaneous) administration. The NEUPOGEN compound is a recombinant methionyl human G-CSF. The NEULASTA, compound is a covalent conjugate of recombinant methionyl human G-CSF and monomethoxypolyethylene glycol. As described above, G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) is an amino acid lengthened and/or glycosylated form of G-CSF.
4.A. Testing for Bioavailability Through ELISA
To evaluate the bioavailability of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), an ELISA analysis was performed on plasma samples obtained from mice that were given doses of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), PEG-G-CSF and rh-G-CSF through i.v. and s.c. administration.
Test and control articles were as follows: partially purified G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), PEG-G-CSF (NEULASTA), rh-G-CSF (NEUPOGEN) and the vehicle control (150 mM NaCl+20 mM NaOAc+0.004% Tween-20); each manufactured in a manner that was acceptable for use in animals via the designated routes of administration, i.v. and s.c.
Mice were given doses of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), PEG-G-CSF, rh-G-CSF (each in the amount of 125 μg/kg) and a vehicle control through i.v and s.c. administration. Mouse plasma samples were isolated. If required, the mouse plasma samples were diluted.
Then, the mouse samples were analyzed with G-CSF ELISA. The main purpose of analyzing the plasma samples via ELISA was for qualitative purposes only, and not for quantitative purposes (i.e., not to obtain extremely precise blood plasma level concentrations). The G-CSF ELISA results either provided a qualitative affirmation that the test article was present in the plasma or a qualitative repudiation that the test article was not in the plasma. The plasma samples were analyzed in triplicate, using two dilutions.
The results were that intravenously administered G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) could be detected out to 72 hours, whereas PEG-G-CSF could only be detected out to 24 hours. In addition, both subcutaneously administered G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) and PEG-G-CSF could be detected out to 72 hours. Subcutaneously administered rh-G-CSF could be detected at the 15-minute and 2-hour sampling time points.
4.B. A Single Dose Comparison of G-CSF-NNT155 (NNT155 Disclosed as SEQ ID NO: 2) and PEG-G-CSF on the Hematopoietic Effects in Mice
In another evaluation of the bioavailability and efficacy of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), hematology analysis involving white blood cell and neutrophil count measurements was performed on plasma samples obtained from mice that were given doses of G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2), PEG-G-CSF and rh-G-CSF through i.v. and s.c. administration.
Test and control articles were the same as for the above G-CSF ELISA evaluation. The procedures for obtaining plasma samples were also the same as for the G-CSF ELISA evaluation. Hematology analysis results were as follows.
The white blood cell count mean data. for the vehicle control ranged from 0.76×103/μL to 4.35×103/μL and 1.27×103/μL to 4.25×103/μL for the i.v. and s.c. administration, respectively. The mean absolute neutrophil count data for the vehicle control ranged from 0.11×103/μL to 0.55×103/μL and 0.29×103/μL to 0.35×103/μL for i.v. and s.c. administration, respectively.
The mean white blood cell count for G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) increased from 1.44×103/μL, 15 minutes post-dose to 11.45×103/μL, 72 hours post i.v. administration. The mean white blood cell count for G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) increased from 3.15×103/μL, 15 minutes post-dose to 11.45×103/μL, 72 hours post s.c. administration. Similarly, mean absolute neutrophil count data for G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) increased from 0.04×103/μL, 15 minutes post-dose to 4.24×103/μL, 72 hours post i.v. administration. The mean absolute neutrophil count for G-CSF-NNT155 (NNT155 disclosed as SEQ ID NO: 2) increased from 0.25×103/μL, at 15 minutes post-dose to 2.04×103/μL, at 72 hours post administration and decreasing to 0.14×103/μL for the s.c. route of administration at 120 hours post administration.
The mean white blood cell count for PEG-G-CSF (NEULASTA) increased from 1.36×103/μL, at 15 minutes post-dose to 6.03×103/μL, at 24 hours post administration, and then decreased to 3.01×103/μL, at 72 hour post i.v. administration. The mean white blood cell count for PEG-G-CSF (NEULASTA) increased from 1.47×103/μL, at 15 minutes post-dose to 4.58×103/μL, at 24 hours post administration, and then decreased to 2.47×103/μL, at 120 hours post s.c. administration. The mean absolute neutrophil count for PEG-G-CSF (NEULASTA) increased from 0.05×103/μL, at 15 minutes post-dose to 1.83×103/μL, at 24 hours post administration, and then decreased to 0.20×103/μL, at 72 hours post i.v. administration. The mean absolute neutrophil count for PEG-G-CSF (NEULASTA) increased from 0.18×103/μL, at 15 minutes post-dose to 1.04×103/μL, at 24 hours post administration and then decreased to 0.22×103/μL, 120 hours post s.c. administration.
The mean white blood cell count for rh-G-CSF (NEUPOGEN) decreased from 1.30×103/μL, at 15 minutes post-dose to 1.19×103/μL at 2 hours post s.c. administration. The mean absolute neutrophil count for rh-G-CSF (NEUPOGEN) increased from 0.11×103/μL, at 15 minutes post-dose to 0.49×103/μL at 2 hours post s.c. route of administration.
The result showed that intravenous administration of G-CSF-NNT155 (disclosed as SEQ ID NO: 2) demonstrated a substantial increase in white blood cell counts, through 72 hours post-dose, which correlated directly to an increase in absolute neutrophil counts. This mean increase exceeded the white blood cell count of the vehicle control by approximately 260%. Similarly, a mean increase in the white blood cell count for the s.c. administration of G-CSF-NNT1.55 (NNT155 disclosed as SEQ ID NO: 2) exceeded that of both the vehicle control and PEG-G-CSF by approximately 295%, 72 hours post-dose. However, both the mean white blood cell count and the mean absolute neutrophil count returned to that of both the vehicle control and PEG-G-CSF at 120 hours post-dose.
In some embodiments, the peptide contains the sequence NNT, NNNNT (SEQ ID NO: 182) or NNNNNT (SEQ ID NO: 183), and n is an integer of about 150 to about 160. In some of these embodiments, the biologically active protein is G-CSF.
All publications cited in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains. All these publications are herein incorporated by reference to the same extent as if each individual publication were specifically and individually indicated as being incorporated by reference.
Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.







TABLE 1





Peptide Motifs having N(Asn) as the Major Constituent


(SEQ ID NOS: 184-904, respectively, in order of appearance)















NNT, TNN, NTN, NNNT, TNNN, NTNN, NNTN, NNNNT, TNNNN, NTNNN,


 


NNTNN, NNNTN, NNNTT, TTNNN, TNTNN, TNNTN, TNNNT, NTTNN,


 


NTNTN, NTNNT, NNTTN, NNTNT, NNNNNT, TNNNNN, NTNNNN, NNTNNN,


 


NNNTNN, NNNNTN, NNNNTT, TTNNNN, TNTNNN, TNNTNN, TNNNTN,


 


TNNNNT, NTTNNN, NTNTNN, NTNNTN, NTNNNT, NNTTNN, NNTNTN,


 


NNTNNT, NNNTTN, NNNTNT, NNNNTTT, TTTNNNN, TNTTNNN, TNTNTNN,


 


TNTNNTN, TNTNNNT, TNNTTNN, TNNTNTN, TNNTNNT, TNNNTNT,


 


TNNNTTN, TNNNNTT, TTNTNNN, TTNNTNN, TTNNNTN, TTNNNNT,


 


NTTTNNN, NTTNTNN, NTTNNTN, NTTNNNT, NTNTTNN, NTNNTTN,


 


NTNNNTT, NTNTNTN, NTNTNNT, NTNNTNT, NNTTTNN, NNTTNTN,


 


NNTTNNT, NNTNTTN, NNTNTNT, NNTNNTT, NNNTTTN, NNNTTNT,


 


NNNTNTT, NNNNNTT, TTNNNNN, TNTNNNN, TNNTNNN, TNNNTNN,


 


TNNNNTN, TNNNNNT, NTTNNNN, NTNTNNN, NTNNTNN, NTNNNTN,


 


NTNNNNT, NNTTNNN, NNTNTNN, NNTNNTN, NNTNNNT, NNNTTNN,


 


NNNTNTN, NNNTNNT, NNNNTTN, NNNNTNT NNNNNNT, TNNNNNN,


 


NTNNNNN, NNTNNNN, NNNTNNN, NNNNTNN, NNNNNTN, NNA, ANN,


 


NAN, NNNA, ANNN, NANN, NNAN, NNNNA, ANNNN, NANNN, NNANN,


 


NNNAN, NNNAA, AANNN, ANANN, ANNAN, ANNNA, NAANN, NANAN,


 


NANNA, NNAAN, NNANA, NNNNNA, ANNNNN, NANNNN, NNANNN,


 


NNNANN, NNNNAN, NNNNAA, AANNNN, ANANNN, ANNANN, ANNNAN,


 


ANNNNA, NAANNN, NANANN, NANNAN, NANNNA, NNAANN, NNANAN,


 


NNANNA, NNNAAN, NNNANA, NNNNAAA, AAANNNN, ANAANNN,


 


ANANANN, ANANNAN, ANANNNA, ANNAANN, ANNANAN, ANNANNA,


 


ANNNANA, ANNNAAN, ANNNNAA, AANANNN, AANNANN, AANNNAN,


 


AANNNNA, NAAANNN, NAANANN, NAANNAN, NAANNNA, NANAANN,


 


NANNAAN, NANNNAA, NANANAN, NANANNA, NANNANA, NNAAANN,


 


NNAANAN, NNAANNA, NNANAAN, NNANANA, NNANNAA, NNNAAAN,


 


NNNAANA, NNNANAA, NNNNNAA, AANNNNN, ANANNNN, ANNANNN,


 


ANNNANN, ANNNNAN, ANNNNNA, NAANNNN, NANANNN, NANNANN,


 


NANNNAN, NANNNNA, NNAANNN, NNANANN, NNANNAN, NNANNNA,


 


NNNAANN, NNNANAN, NNNANNA, NNNNAAN, NNNNANA NNNNNNA,


 


ANNNNNN, NANNNNN, NNANNNN, NNNANNN, NNNNANN, NNNNNAN,


 


NNS, SNN, NSN, NNNS, SNNN, NSNN, NNSN, NNNNS, SNNNN, NSNNN,


 


NNSNN, NNNSN, NNNSS, SSNNN, SNSNN, SNNSN, SNNNS, NSSNN, NSNSN,


 


NSNNS, NNSSN, NNSNS, NNNNNS, SNNNNN, NSNNNN, NNSNNN, NNNSNN,


 


NNNNSN, NNNNSS, SSNNNN, SNSNNN, SNNSNN, SNNNSN, SNNNNS,


 


NSSNNN, NSNSNN, NSNNSN, NSNNNS, NNSSNN, NNSNSN, NNSNNS,


 


NNNSSN, NNNSNS, NNNNSSS, SSSNNNN, SNSSNNN, SNSNSNN, SNSNNSN,


 


SNSNNNS, SNNSSNN, SNNSNSN, SNNSNNS, SNNNSNS, SNNNSSN,


 


SNNNNSS, SSNSNNN, SSNNSNN, SSNNNSN, SSNNNNS, NSSSNNN,


 


NSSNSNN, NSSNNSN, NSSNNNS, NSNSSNN, NSNNSSN, NSNNNSS,


 


NSNSNSN, NSNSNNS, NSNNSNS, NNSSSNN, NNSSNSN, NNSSNNS,


 


NNSNSSN, NNSNSNS, NNSNNSS, NNNSSSN, NNNSSNS, NNNSNSS,


 


NNNNNSS, SSNNNNN, SNSNNNN, SNNSNNN, SNNNSNN, SNNNNSN,


 


SNNNNNS, NSSNNNN, NSNSNNN, NSNNSNN, NSNNNSN, NSNNNNS,


 


NNSSNNN, NNSNSNN, NNSNNSN, NNSNNNS, NNNSSNN, NNNSNSN,


 


NNNSNNS, NNNNSSN, NNNNSNS NNNNNNS, SNNNNNN, NSNNNNN,


 


NNSNNNN, NNNSNNN, NNNNSNN, NNNNNSN, NNQ, QNN, NQN, NNNQ,


 


QNNN, NQNN, NNQN, NNNNQ, QNNNN, NQNNN, NNQNN, NNNQN, NNNQQ,


 


QQNNN, QNQNN, QNNQN, QNNNQ, NQQNN, NQNQN, NQNNQ, NNQQN,


 


NNQNQ, NNNNNQ, QNNNNN, NQNNNN, NNQNNN, NNNQNN, NNNNQN,


 


NNNNQQ, QQNNNN, QNQNNN, QNNQNN, QNNNQN, QNNNNQ, NQQNNN,


 


NQNQNN, NQNNQN, NQNNNQ, NNQQNN, NNQNQN, NNQNNQ, NNNQQN,


 


NNNQNQ, NNNNQQQ, QQQNNNN, QNQQNNN, QNQNQNN, QNQNNQN,


 


QNQNNNQ, QNNQQNN, QNNQNQN, QNNQNNQ, QNNNQNQ, QNNNQQN,


 


QNNNNQQ, QQNQNNN, QQNNQNN, QQNNNQN, QQNNNNQ, NQQQNNN,


 


NQQNQNN, NQQNNQN, NQQNNNQ, NQNQQNN, NQNNQQN, NQNNNQQ,


 


NQNQNQN, NQNQNNQ, NQNNQNQ, NNQQQNN, NNQQNQN, NNQQNNQ,


 


NNQNQQN, NNQNQNQ, NNQNNQQ, NNNQQQN, NNNQQNQ, NNNQNQQ,


 


NNNNNQQ, QQNNNNN, QNQNNNN, QNNQNNN, QNNNQNN, QNNNNQN,


 


QNNNNNQ, NQQNNNN, NQNQNNN, NQNNQNN, NQNNNQN, NQNNNNQ,


 


NNQQNNN, NNQNQNN, NNQNNQN, NNQNNNQ, NNNQQNN, NNNQNQN,


 


NNNQNNQ, NNNNQQN, NNNNQNQ NNNNNNQ, QNNNNNN, NQNNNNN,


 


NNQNNNN, NNNQNNN, NNNNQNN, NNNNNQN, NNE, ENN, NEN, NNNE,


 


ENNN, NENN, NNEN, NNNNE, ENNNN, NENNN, NNENN, NNNEN, NNNEE,


 


EENNN, ENENN, ENNEN, ENNNE, NEENN, NENEN, NENNE, NNEEN,


 


NNENE, NNNNNE, ENNNNN, NENNNN, NNENNN, NNNENN, NNNNEN,


 


NNNNEE, EENNNN, ENENNN, ENNENN, ENNNEN, ENNNNE, NEENNN,


 


NENENN, NENNEN, NENNNE, NNEENN, NNENEN, NNENNE, NNNEEN,


 


NNNENE, NNNNEEE, EEENNNN, ENEENNN, ENENENN, ENENNEN,


 


ENENNNE, ENNEENN, ENNENEN, ENNENNE, ENNNENE, ENNNEEN,


 


ENNNNEE, EENENNN, EENNENN, EENNNEN, EENNNNE, NEEENNN,


 


NEENENN, NEENNEN, NEENNNE, NENEENN, NENNEEN, NENNNEE,


 


NENENEN, NENENNE, NENNENE, NNEEENN, NNEENEN, NNEENNE,


 


NNENEEN, NNENENE, NNENNEE, NNNEEEN, NNNEENE, NNNENEE,


 


NNNNNEE, EENNNNN, ENENNNN, ENNENNN, ENNNENN, ENNNNEN,


 


ENNNNNE, NEENNNN, NENENNN, NENNENN, NENNNEN, NENNNNE,


 


NNEENNN, NNENENN, NNENNEN, NNENNNE, NNNEENN, NNNENEN,


 


NNNENNE, NNNNEEN, NNNNENE NNNNNNE, ENNNNNN, NENNNNN,


 


NNENNNN, NNNENNN, NNNNENN, NNNNNEN, NNH, HNN, NHN, NNNH,


 


HNNN, NHNN, NNHN, NNNNH, HNNNN, NHNNN, NNHNN, NNNHN, NNNHH,


 


HHNNN, HNHNN, HNNHN, HNNNH, NHHNN, NHNHN, NHNNH, NNHHN,


 


NNHNH, NNNNNH, HNNNNN, NHNNNN, NNHNNN, NNNHNN, NNNNHN,


 


NNNNHH, HHNNNN, HNHNNN, HNNHNN, HNNNHN, HNNNNH, NHHNNN,


 


NHNHNN, NHNNHN, NHNNNH, NNHHNN, NNHNHN, NNHNNH, NNNHHN,


 


NNNHNH, NNNNHHH, HHHNNNN, HNHHNNN, HNHNHNN, HNHNNHN,


 


HNHNNNH, HNNHHNN, HNNHNHN, HNNHNNH, HNNNHNH, HNNNHHN,


 


HNNNNHH, HHNHNNN, HHNNHNN, HHNNNHN, HHNNNNH, NHHHNNN,


 


NHHNHNN, NHHNNHN, NHHNNNH, NHNHHNN, NHNNHHN, NHNNNHH,


 


NHNHNHN, NHNHNNH, NHNNHNH, NNHHHNN, NNHHNHN, NNHHNNH,


 


NNHNHHN, NNHNHNH, NNHNNHH, NNNHHHN, NNNHHNH, NNNHNHH,


 


NNNNNHH, HHNNNNN, HNHNNNN, HNNHNNN, HNNNHNN, HNNNNHN,


 


HNNNNNH, NHHNNNN, NHNHNNN, NHNNHNN, NHNNNHN, NHNNNNH,


 


NNHHNNN, NNHNHNN, NNHNNHN, NNHNNNH, NNNHHNN, NNNHNHN,


 


NNNHNNH, NNNNHHN, NNNNHNH NNNNNNH, HNNNNNN, NHNNNNN,


 


NNHNNNN, NNNHNNN, NNNNHNN, NNNNNHN, NND, DNN, NDN, NNND,


 


DNNN, NDNN, NNDN, NNNND, DNNNN, NDNNN, NNDNN, NNNDN, NNNDD,


 


DDNNN, DNDNN, DNNDN, DNNND, NDDNN, NDNDN, NDNND, NNDDN,


 


NNDND, NNNNND, DNNNNN, NDNNNN, NNDNNN, NNNDNN, NNNNDN,


 


NNNNDD, DDNNNN, DNDNNN, DNNDNN, DNNNDN, DNNNND, NDDNNN,


 


NDNDNN, NDNNDN, NDNNND, NNDDNN, NNDNDN, NNDNND, NNNDDN,


 


NNNDND, NNNNDDD, DDDNNNN, DNDDNNN, DNDNDNN, DNDNNDN,


 


DNDNNND, DNNDDNN, DNNDNDN, DNNDNND, DNNNDND, DNNNDDN,


 


DNNNNDD, DDNDNNN, DDNNDNN, DDNNNDN, DDNNNND, NDDDNNN,


 


NDDNDNN, NDDNNDN, NDDNNND, NDNDDNN, NDNNDDN, NDNNNDD,


 


NDNDNDN, NDNDNND, NDNNDND, NNDDDNN, NNDDNDN, NNDDNND,


 


NNDNDDN, NNDNDND, NNDNNDD, NNNDDDN, NNNDDND, NNNDNDD,


 


NNNNNDD, DDNNNNN, DNDNNNN, DNNDNNN, DNNNDNN, DNNNNDN,


 


DNNNNND, NDDNNNN, NDNDNNN, NDNNDNN, NDNNNDN, NDNNNND,


 


NNDDNNN, NNDNDNN, NNDNNDN, NNDNNND, NNNDDNN, NNNDNDN,


 


NNNDNND, NNNNDDN, NNNNDND NNNNNND, DNNNNNN, NDNNNNN,


 


NNDNNNN, NNNDNNN, NNNNDNN, and NNNNNDN.
















TABLE 2





Peptide Motifs having G (Gly) as the Major Constituent


(SEQ ID NOS: 905-1728, respectively, in order of appearance)















GGT, TGG, GTG, GGGT, TGGG, GTGG, GGTG, GGGGT, TGGGG, GTGGG,


 


GGTGG, GGGTG, GGGTT, TTGGG, TGTGG, TGGTG, TGGGT, GTTGG,


 


GTGTG, GTGGT, GGTTG, GGTGT, GGGGGT, TGGGGG, GTGGGG, GGTGGG,


 


GGGTGG, GGGGTG, GGGGTT, TTGGGG, TGTGGG, TGGTGG, TGGGTG,


 


TGGGGT, GTTGGG, GTGTGG, GTGGTG, GTGGGT, GGTTGG, GGTGTG,


 


GGTGGT, GGGTTG, GGGTGT, GGGGTTT, TTTGGGG, TGTTGGG, TGTGTGG,


 


TGTGGTG, TGTGGGT, TGGTTGG, TGGTGTG, TGGTGGT, TGGGTGT,


 


TGGGTTG, TGGGGTT, TTGTGGG, TTGGTGG, TTGGGTG, TTGGGGT,


 


GTTTGGG, GTTGTGG, GTTGGTG, GTTGGGT, GTGTTGG, GTGGTTG,


 


GTGGGTT, GTGTGTG, GTGTGGT, GTGGTGT, GGTTTGG, GGTTGTG,


 


GGTTGGT, GGTGTTG, GGTGTGT, GGTGGTT, GGGTTTG, GGGTTGT,


 


GGGTGTT, GGGGGTT, TTGGGGG, TGTGGGG, TGGTGGG, TGGGTGG,


 


TGGGGTG, TGGGGGT, GTTGGGG, GTGTGGG, GTGGTGG, GTGGGTG,


 


GTGGGGT, GGTTGGG, GGTGTGG, GGTGGTG, GGTGGGT, GGGTTGG,


 


GGGTGTG, GGGTGGT, GGGGTTG, GGGGTGT GGGGGGT, TGGGGGG,


 


GTGGGGG, GGTGGGG, GGGTGGG, GGGGTGG, GGGGGTG, GGA, AGG,


 


GAG, GGGA, AGGG, GAGG, GGAG, GGGGA, AGGGG, GAGGG, GGAGG,


 


GGGAG, GGGAA, AAGGG, AGAGG, AGGAG, AGGGA, GAAGG, GAGAG,


 


GAGGA, GGAAG, GGAGA, GGGGGA, AGGGGG, GAGGGG, GGAGGG,


 


GGGAGG, GGGGAG, GGGGAA, AAGGGG, AGAGGG, AGGAGG, AGGGAG,


 


AGGGGA, GAAGGG, GAGAGG, GAGGAG, GAGGGA, GGAAGG, GGAGAG,


 


GGAGGA, GGGAAG, GGGAGA, GGGGAAA, AAAGGGG, AGAAGGG,


 


AGAGAGG, AGAGGAG, AGAGGGA, AGGAAGG, AGGAGAG, AGGAGGA,


 


AGGGAGA, AGGGAAG, AGGGGAA, AAGAGGG, AAGGAGG, AAGGGAG,


 


AAGGGGA, GAAAGGG, GAAGAGG, GAAGGAG, GAAGGGA, GAGAAGG,


 


GAGGAAG, GAGGGAA, GAGAGAG, GAGAGGA, GAGGAGA, GGAAAGG,


 


GGAAGAG, GGAAGGA, GGAGAAG, GGAGAGA, GGAGGAA, GGGAAAG,


 


GGGAAGA, GGGAGAA, GGGGGAA, AAGGGGG, AGAGGGG, AGGAGGG,


 


AGGGAGG, AGGGGAG, AGGGGGA, GAAGGGG, GAGAGGG, GAGGAGG,


 


GAGGGAG, GAGGGGA, GGAAGGG, GGAGAGG, GGAGGAG, GGAGGGA,


 


GGGAAGG, GGGAGAG, GGGAGGA, GGGGAAG, GGGGAGA GGGGGGA,


 


AGGGGGG, GAGGGGG, GGAGGGG, GGGAGGG, GGGGAGG, GGGGGAG,


 


GGS, SGG, GSG, GGGS, SGGG, GSGG, GGSG, GGGGS, SGGGG, GSGGG,


 


GGSGG, GGGSG, GGGSS, SSGGG, SGSGG, SGGSG, SGGGS, GSSGG, GSGSG,


 


GSGGS, GGSSG, GGSGS, GGGGGS, SGGGGG, GSGGGG, GGSGGG, GGGSGG,


 


GGGGSG, GGGGSS, SSGGGG, SGSGGG, SGGSGG, SGGGSG, SGGGGS,


 


GSSGGG, GSGSGG, GSGGSG, GSGGGS, GGSSGG, GGSGSG, GGSGGS,


 


GGGSSG, GGGSGS, GGGGSSS, SSSGGGG, SGSSGGG, SGSGSGG, SGSGGSG,


 


SGSGGGS, SGGSSGG, SGGSGSG, SGGSGGS, SGGGSGS, SGGGSSG,


 


SGGGGSS, SSGSGGG, SSGGSGG, SSGGGSG, SSGGGGS, GSSSGGG,


 


GSSGSGG, GSSGGSG, GSSGGGS, GSGSSGG, GSGGSSG, GSGGGSS,


 


GSGSGSG, GSGSGGS, GSGGSGS, GGSSSGG, GGSSGSG, GGSSGGS,


 


GGSGSSG, GGSGSGS, GGSGGSS, GGGSSSG, GGGSSGS, GGGSGSS,


 


GGGGGSS, SSGGGGG, SGSGGGG, SGGSGGG, SGGGSGG, SGGGGSG,


 


SGGGGGS, GSSGGGG, GSGSGGG, GSGGSGG, GSGGGSG, GSGGGGS,


 


GGSSGGG, GGSGSGG, GGSGGSG, GGSGGGS, GGGSSGG, GGGSGSG,


 


GGGSGGS, GGGGSSG, GGGGSGS, GGGGGGS, SGGGGGG, GSGGGGG,


 


GGSGGGG, GGGSGGG, GGGGSGG, GGGGGSG, GGQ, QGG, GQG, GGGQ,


 


QGGG, GQGG, GGQG, GGGGQ, QGGGG, GQGGG, GGQGG, GGGQG, GGGQQ,


 


QQGGG, QGQGG, QGGQG, QGGGQ, GQQGG, GQGQG, GQGGQ, GGQQG,


 


GGQGQ, GGGGGQ, QGGGGG, GQGGGG, GGQGGG, GGGQGG, GGGGQG,


 


GGGGQQ, QQGGGG, QGQGGG, QGGQGG, QGGGQG, QGGGGQ, GQQGGG,


 


GQGQGG, GQGGQG, GQGGGQ, GGQQGG, GGQGQG, GGQGGQ, GGGQQG,


 


GGGQGQ, GGGGQQQ, QQQGGGG, QGQQGGG, QGQGQGG, QGQGGQG,


 


QGQGGGQ, QGGQQGG, QGGQGQG, QGGQGGQ, QGGGQGQ, QGGGQQG,


 


QGGGGQQ, QQGQGGG, QQGGQGG, QQGGGQG, QQGGGGQ, GQQQGGG,


 


GQQGQGG, GQQGGQG, GQQGGGQ, GQGQQGG, GQGGQQG, GQGGGQQ,


 


GQGQGQG, GQGQGGQ, GQGGQGQ, GGQQQGG, GGQQGQG, GGQQGGQ,


 


GGQGQQG, GGQGQGQ, GGQGGQQ, GGGQQQG, GGGQQGQ, GGGQGQQ,


 


GGGGGQQ, QQGGGGG, QGQGGGG, QGGQGGG, QGGGQGG, QGGGGQG,


 


QGGGGGQ, GQQGGGG, GQGQGGG, GQGGQGG, GQGGGQG, GQGGGGQ,


 


GGQQGGG, GGQGQGG, GGQGGQG, GGQGGGQ, GGGQQGG, GGGQGQG,


 


GGGQGGQ, GGGGQQG, GGGGQGQ GGGGGGQ, QGGGGGG, GQGGGGG,


 


GGQGGGG, GGGQGGG, GGGGQGG, GGGGGQG, GGE, EGG, GEG, GGGE,


 


EGGG, GEGG, GGEG, GGGGE, EGGGG, GEGGG, GGEGG, GGGEG, GGGEE,


 


EEGGG, EGEGG, EGGEG, EGGGE, GEEGG, GEGEG, GEGGE, GGEEG,


 


GGEGE, GGGGGE, EGGGGG, GEGGGG, GGEGGG, GGGEGG, GGGGEG,


 


GGGGEE, EEGGGG, EGEGGG, EGGEGG, EGGGEG, EGGGGE, GEEGGG,


 


GEGEGG, GEGGEG, GEGGGE, GGEEGG, GGEGEG, GGEGGE, GGGEEG,


 


GGGEGE, GGGGEEE, EEEGGGG, EGEEGGG, EGEGEGG, EGEGGEG,


 


EGEGGGE, EGGEEGG, EGGEGEG, EGGEGGE, EGGGEGE, EGGGEEG,


 


EGGGGEE, EEGEGGG, EEGGEGG, EEGGGEG, EEGGGGE, GEEEGGG,


 


GEEGEGG, GEEGGEG, GEEGGGE, GEGEEGG, GEGGEEG, GEGGGEE,


 


GEGEGEG, GEGEGGE, GEGGEGE, GGEEEGG, GGEEGEG, GGEEGGE,


 


GGEGEEG, GGEGEGE, GGEGGEE, GGGEEEG, GGGEEGE, GGGEGEE,


 


GGGGGEE, EEGGGGG, EGEGGGG, EGGEGGG, EGGGEGG, EGGGGEG,


 


EGGGGGE, GEEGGGG, GEGEGGG, GEGGEGG, GEGGGEG, GEGGGGE,


 


GGEEGGG, GGEGEGG, GGEGGEG, GGEGGGE, GGGEEGG, GGGEGEG,


 


GGGEGGE, GGGGEEG, GGGGEGE GGGGGGE, EGGGGGG, GEGGGGG,


 


GGEGGGG, GGGEGGG, GGGGEGG, GGGGGEG, GGH, HGG, GHG, GGGH,


 


HGGG, GHGG, GGHG, GGGGH, HGGGG, GHGGG, GGHGG, GGGHG, GGGHH,


 


HHGGG, HGHGG, HGGHG, HGGGH, GHHGG, GHGHG, GHGGH, GGHHG,


 


GGHGH, GGGGGH, HGGGGG, GHGGGG, GGHGGG, GGGHGG, GGGGHG,


 


GGGGHH, HHGGGG, HGHGGG, HGGHGG, HGGGHG, HGGGGH, GHHGGG,


 


GHGHGG, GHGGHG, GHGGGH, GGHHGG, GGHGHG, GGHGGH, GGGHHG,


 


GGGHGH, GGGGHHH, HHHGGGG, HGHHGGG, HGHGHGG, HGHGGHG,


 


HGHGGGH, HGGHHGG, HGGHGHG, HGGHGGH, HGGGHGH, HGGGHHG,


 


HGGGGHH, HHGHGGG, HHGGHGG, HHGGGHG, HHGGGGH, GHHHGGG,


 


GHHGHGG, GHHGGHG, GHHGGGH, GHGHHGG, GHGGHHG, GHGGGHH,


 


GHGHGHG, GHGHGGH, GHGGHGH, GGHHHGG, GGHHGHG, GGHHGGH,


 


GGHGHHG, GGHGHGH, GGHGGHH, GGGHHHG, GGGHHGH, GGGHGHH,


 


GGGGGHH, HHGGGGG, HGHGGGG, HGGHGGG, HGGGHGG, HGGGGHG,


 


HGGGGGH, GHHGGGG, GHGHGGG, GHGGHGG, GHGGGHG, GHGGGGH,


 


GGHHGGG, GGHGHGG, GGHGGHG, GGHGGGH, GGGHHGG, GGGHGHG,


 


GGGHGGH, GGGGHHG, GGGGHGH GGGGGGH, HGGGGGG, GHGGGGG,


 


GGHGGGG, GGGHGGG, GGGGHGG, GGGGGHG, GGN, NGG, GNG, GGGN,


 


NGGG, GNGG, GGNG, GGGGN, NGGGG, GNGGG, GGNGG, GGGNG, GGGNN,


 


NNGGG, NGNGG, NGGNG, NGGGN, GNNGG, GNGNG, GNGGN, GGNNG,


 


GGNGN, GGGGGN, NGGGGG, GNGGGG, GGNGGG, GGGNGG, GGGGNG,


 


GGGGNN, NNGGGG, NGNGGG, NGGNGG, NGGGNG, NGGGGN, GNNGGG,


 


GNGNGG, GNGGNG, GNGGGN, GGNNGG, GGNGNG, GGNGGN, GGGNNG,


 


GGGNGN, GGGGNNN, NNNGGGG, NGNNGGG, NGNGNGG, NGNGGNG,


 


NGNGGGN, NGGNNGG, NGGNGNG, NGGNGGN, NGGGNGN, NGGGNNG,


 


NGGGGNN, NNGNGGG, NNGGNGG, NNGGGNG, NNGGGGN, GNNNGGG,


 


GNNGNGG, GNNGGNG, GNNGGGN, GNGNNGG, GNGGNNG, GNGGGNN,


 


GNGNGNG, GNGNGGN, GNGGNGN, GGNNNGG, GGNNGNG, GGNNGGN,


 


GGNGNNG, GGNGNGN, GGNGGNN, GGGNNNG, GGGNNGN, GGGNGNN,


 


GGGGGNN, NNGGGGG, NGNGGGG, NGGNGGG, NGGGNGG, NGGGGNG,


 


NGGGGGN, GNNGGGG, GNGNGGG, GNGGNGG, GNGGGNG, GNGGGGN,


 


GGNNGGG, GGNGNGG, GGNGGNG, GGNGGGN, GGGNNGG, GGGNGNG,


 


GGGNGGN, GGGGNNG, GGGGNGN GGGGGGN, NGGGGGG, GNGGGGG,


 


GGNGGGG, GGGNGGG, GGGGNGG, GGGGGNG, GGD, DGG, GDG, GGGD,


 


DGGG, GDGG, GGDG, GGGGD, DGGGG, GDGGG, GGDGG, GGGDG, GGGDD,


 


DDGGG, DGDGG, DGGDG, DGGGD, GDDGG, GDGDG, GDGGD, GGDDG,


 


GGDGD, GGGGGD, DGGGGG, GDGGGG, GGDGGG, GGGDGG, GGGGDG,


 


GGGGDD, DDGGGG, DGDGGG, DGGDGG, DGGGDG, DGGGGD, GDDGGG,


 


GDGDGG, GDGGDG, GDGGGD, GGDDGG, GGDGDG, GGDGGD, GGGDDG,


 


GGGDGD, GGGGDDD, DDDGGGG, DGDDGGG, DGDGDGG, DGDGGDG,


 


DGDGGGD, DGGDDGG, DGGDGDG, DGGDGGD, DGGGDGD, DGGGDDG,


 


DGGGGDD, DDGDGGG, DDGGDGG, DDGGGDG, DDGGGGD, GDDDGGG,


 


GDDGDGG, GDDGGDG, GDDGGGD, GDGDDGG, GDGGDDG, GDGGGDD,


 


GDGDGDG, GDGDGGD, GDGGDGD, GGDDDGG, GGDDGDG, GGDDGGD,


 


GGDGDDG, GGDGDGD, GGDGGDD, GGGDDDG, GGGDDGD, GGGDGDD,


 


GGGGGDD, DDGGGGG, DGDGGGG, DGGDGGG, DGGGDGG, DGGGGDG,


 


DGGGGGD, GDDGGGG, GDGDGGG, GDGGDGG, GDGGGDG, GDGGGGD,


 


GGDDGGG, GGDGDGG, GGDGGDG, GGDGGGD, GGGDDGG, GGGDGDG,


 


GGGDGGD, GGGGDDG, GGGGDGD GGGGGGD, DGGGGGG, GDGGGGG,


 


GGDGGGG, GGGDGGG, GGGGDGG, and GGGGGDG.
















TABLE 3





Peptide Motifs having Q (Gln) as the Major Constituent


(SEQ ID NOS: 1729-2449, respectively, in order of appearance)















QQT, TQQ, QTQ, QQQT, TQQQ, QTQQ, QQTQ, QQQQT, TQQQQ, QTQQQ,


 


QQTQQ, QQQTQ, QQQTT, TTQQQ, TQTQQ, TQQTQ, TQQQT, QTTQQ,


 


QTQTQ, QTQQT, QQTTQ, QQTQT, QQQQQT, TQQQQQ, QTQQQQ, QQTQQQ,


 


QQQTQQ, QQQQTQ, QQQQTT, TTQQQQ, TQTQQQ, TQQTQQ, TQQQTQ,


 


TQQQQT, QTTQQQ, QTQTQQ, QTQQTQ, QTQQQT, QQTTQQ, QQTQTQ,


 


QQTQQT, QQQTTQ, QQQTQT, QQQQTTT, TTTQQQQ, TQTTQQQ, TQTQTQQ,


 


TQTQQTQ, TQTQQQT, TQQTTQQ, TQQTQTQ, TQQTQQT, TQQQTQT,


 


TQQQTTQ, TQQQQTT, TTQTQQQ, TTQQTQQ, TTQQQTQ, TTQQQQT,


 


QTTTQQQ, QTTQTQQ, QTTQQTQ, QTTQQQT, QTQTTQQ, QTQQTTQ,


 


QTQQQTT, QTQTQTQ, QTQTQQT, QTQQTQT, QQTTTQQ, QQTTQTQ,


 


QQTTQQT, QQTQTTQ, QQTQTQT, QQTQQTT, QQQTTTQ, QQQTTQT,


 


QQQTQTT, QQQQQTT, TTQQQQQ, TQTQQQQ, TQQTQQQ, TQQQTQQ,


 


TQQQQTQ, TQQQQQT, QTTQQQQ, QTQTQQQ, QTQQTQQ, QTQQQTQ,


 


QTQQQQT, QQTTQQQ, QQTQTQQ, QQTQQTQ, QQTQQQT, QQQTTQQ,


 


QQQTQTQ, QQQTQQT, QQQQTTQ, QQQQTQT QQQQQQT, TQQQQQQ,


 


QTQQQQQ, QQTQQQQ, QQQTQQQ, QQQQTQQ, QQQQQTQ, QQA, AQQ,


 


QAQ, QQQA, AQQQ, QAQQ, QQAQ, QQQQA, AQQQQ, QAQQQ, QQAQQ,


 


QQQAQ, QQQAA, AAQQQ, AQAQQ, AQQAQ, AQQQA, QAAQQ, QAQAQ,


 


QAQQA, QQAAQ, QQAQA, QQQQQA, AQQQQQ, QAQQQQ, QQAQQQ,


 


QQQAQQ, QQQQAQ, QQQQAA, AAQQQQ, AQAQQQ, AQQAQQ, AQQQAQ,


 


AQQQQA, QAAQQQ, QAQAQQ, QAQQAQ, QAQQQA, QQAAQQ, QQAQAQ,


 


QQAQQA, QQQAAQ, QQQAQA, QQQQAAA, AAAQQQQ, AQAAQQQ,


 


AQAQAQQ, AQAQQAQ, AQAQQQA, AQQAAQQ, AQQAQAQ, AQQAQQA,


 


AQQQAQA, AQQQAAQ, AQQQQAA, AAQAQQQ, AAQQAQQ, AAQQQAQ,


 


AAQQQQA, QAAAQQQ, QAAQAQQ, QAAQQAQ, QAAQQQA, QAQAAQQ,


 


QAQQAAQ, QAQQQAA, QAQAQAQ, QAQAQQA, QAQQAQA, QQAAAQQ,


 


QQAAQAQ, QQAAQQA, QQAQAAQ, QQAQAQA, QQAQQAA, QQQAAAQ,


 


QQQAAQA, QQQAQAA, QQQQQAA, AAQQQQQ, AQAQQQQ, AQQAQQQ,


 


AQQQAQQ, AQQQQAQ, AQQQQQA, QAAQQQQ, QAQAQQQ, QAQQAQQ,


 


QAQQQAQ, QAQQQQA, QQAAQQQ, QQAQAQQ, QQAQQAQ, QQAQQQA,


 


QQQAAQQ, QQQAQAQ, QQQAQQA, QQQQAAQ, QQQQAQA QQQQQQA,


 


AQQQQQQ, QAQQQQQ, QQAQQQQ, QQQAQQQ, QQQQAQQ, QQQQQAQ,


 


QQS, SQQ, QSQ, QQQS, SQQQ, QSQQ, QQSQ, QQQQS, SQQQQ, QSQQQ,


 


QQSQQ, QQQSQ, QQQSS, SSQQQ, SQSQQ, SQQSQ, SQQQS, QSSQQ, QSQSQ,


 


QSQQS, QQSSQ, QQSQS, QQQQQS, SQQQQQ, QSQQQQ, QQSQQQ, QQQSQQ,


 


QQQQSQ, QQQQSS, SSQQQQ, SQSQQQ, SQQSQQ, SQQQSQ, SQQQQS,


 


QSSQQQ, QSQSQQ, QSQQSQ, QSQQQS, QQSSQQ, QQSQSQ, QQSQQS,


 


QQQSSQ, QQQSQS, QQQQSSS, SSSQQQQ, SQSSQQQ, SQSQSQQ, SQSQQSQ,


 


SQSQQQS, SQQSSQQ, SQQSQSQ, SQQSQQS, SQQQSQS, SQQQSSQ,


 


SQQQQSS, SSQSQQQ, SSQQSQQ, SSQQQSQ, SSQQQQS, QSSSQQQ,


 


QSSQSQQ, QSSQQSQ, QSSQQQS, QSQSSQQ, QSQQSSQ, QSQQQSS,


 


QSQSQSQ, QSQSQQS, QSQQSQS, QQSSSQQ, QQSSQSQ, QQSSQQS,


 


QQSQSSQ, QQSQSQS, QQSQQSS, QQQSSSQ, QQQSSQS, QQQSQSS,


 


QQQQQSS, SSQQQQQ, SQSQQQQ, SQQSQQQ, SQQQSQQ, SQQQQSQ,


 


SQQQQQS, QSSQQQQ, QSQSQQQ, QSQQSQQ, QSQQQSQ, QSQQQQS,


 


QQSSQQQ, QQSQSQQ, QQSQQSQ, QQSQQQS, QQQSSQQ, QQQSQSQ,


 


QQQSQQS, QQQQSSQ, QQQQSQS QQQQQQS, SQQQQQQ, QSQQQQQ,


 


QQSQQQQ, QQQSQQQ, QQQQSQQ, QQQQQSQ, QQE, EQQ, QEQ, QQQE,


 


EQQQ, QEQQ, QQEQ, QQQQE, EQQQQ, QEQQQ, QQEQQ, QQQEQ, QQQEE,


 


EEQQQ, EQEQQ, EQQEQ, EQQQE, QEEQQ, QEQEQ, QEQQE, QQEEQ,


 


QQEQE, QQQQQE, EQQQQQ, QEQQQQ, QQEQQQ, QQQEQQ, QQQQEQ,


 


QQQQEE, EEQQQQ, EQEQQQ, EQQEQQ, EQQQEQ, EQQQQE, QEEQQQ,


 


QEQEQQ, QEQQEQ, QEQQQE, QQEEQQ, QQEQEQ, QQEQQE, QQQEEQ,


 


QQQEQE, QQQQEEE, EEEQQQQ, EQEEQQQ, EQEQEQQ, EQEQQEQ,


 


EQEQQQE, EQQEEQQ, EQQEQEQ, EQQEQQE, EQQQEQE, EQQQEEQ,


 


EQQQQEE, EEQEQQQ, EEQQEQQ, EEQQQEQ, EEQQQQE, QEEEQQQ,


 


QEEQEQQ, QEEQQEQ, QEEQQQE, QEQEEQQ, QEQQEEQ, QEQQQEE,


 


QEQEQEQ, QEQEQQE, QEQQEQE, QQEEEQQ, QQEEQEQ, QQEEQQE,


 


QQEQEEQ, QQEQEQE, QQEQQEE, QQQEEEQ, QQQEEQE, QQQEQEE,


 


QQQQQEE, EEQQQQQ, EQEQQQQ, EQQEQQQ, EQQQEQQ, EQQQQEQ,


 


EQQQQQE, QEEQQQQ, QEQEQQQ, QEQQEQQ, QEQQQEQ, QEQQQQE,


 


QQEEQQQ, QQEQEQQ, QQEQQEQ, QQEQQQE, QQQEEQQ, QQQEQEQ,


 


QQQEQQE, QQQQEEQ, QQQQEQE QQQQQQE, EQQQQQQ, QEQQQQQ,


 


QQEQQQQ, QQQEQQQ, QQQQEQQ, QQQQQEQ, QQH, HQQ, QHQ, QQQH,


 


HQQQ, QHQQ, QQHQ, QQQQH, HQQQQ, QHQQQ, QQHQQ, QQQHQ, QQQHH,


 


HHQQQ, HQHQQ, HQQHQ, HQQQH, QHHQQ, QHQHQ, QHQQH, QQHHQ,


 


QQHQH, QQQQQH, HQQQQQ, QHQQQQ, QQHQQQ, QQQHQQ, QQQQHQ,


 


QQQQHH, HHQQQQ, HQHQQQ, HQQHQQ, HQQQHQ, HQQQQH, QHHQQQ,


 


QHQHQQ, QHQQHQ, QHQQQH, QQHHQQ, QQHQHQ, QQHQQH, QQQHHQ,


 


QQQHQH, QQQQHHH, HHHQQQQ, HQHHQQQ, HQHQHQQ, HQHQQHQ,


 


HQHQQQH, HQQHHQQ, HQQHQHQ, HQQHQQH, HQQQHQH, HQQQHHQ,


 


HQQQQHH, HHQHQQQ, HHQQHQQ, HHQQQHQ, HHQQQQH, QHHHQQQ,


 


QHHQHQQ, QHHQQHQ, QHHQQQH, QHQHHQQ, QHQQHHQ, QHQQQHH,


 


QHQHQHQ, QHQHQQH, QHQQHQH, QQHHHQQ, QQHHQHQ, QQHHQQH,


 


QQHQHHQ, QQHQHQH, QQHQQHH, QQQHHHQ, QQQHHQH, QQQHQHH,


 


QQQQQHH, HHQQQQQ, HQHQQQQ, HQQHQQQ, HQQQHQQ, HQQQQHQ,


 


HQQQQQH, QHHQQQQ, QHQHQQQ, QHQQHQQ, QHQQQHQ, QHQQQQH,


 


QQHHQQQ, QQHQHQQ, QQHQQHQ, QQHQQQH, QQQHHQQ, QQQHQHQ,


 


QQQHQQH, QQQQHHQ, QQQQHQH QQQQQQH, HQQQQQQ, QHQQQQQ,


 


QQHQQQQ, QQQHQQQ, QQQQHQQ, QQQQQHQ, QQN, NQQ, QNQ, QQQN,


 


NQQQ, QNQQ, QQNQ, QQQQN, NQQQQ, QNQQQ, QQNQQ, QQQNQ, QQQNN,


 


NNQQQ, NQNQQ, NQQNQ, NQQQN, QNNQQ, QNQNQ, QNQQN, QQNNQ,


 


QQNQN, QQQQQN, NQQQQQ, QNQQQQ, QQNQQQ, QQQNQQ, QQQQNQ,


 


QQQQNN, NNQQQQ, NQNQQQ, NQQNQQ, NQQQNQ, NQQQQN, QNNQQQ,


 


QNQNQQ, QNQQNQ, QNQQQN, QQNNQQ, QQNQNQ, QQNQQN, QQQNNQ,


 


QQQNQN, QQQQNNN, NNNQQQQ, NQNNQQQ, NQNQNQQ, NQNQQNQ,


 


NQNQQQN, NQQNNQQ, NQQNQNQ, NQQNQQN, NQQQNQN, NQQQNNQ,


 


NQQQQNN, NNQNQQQ, NNQQNQQ, NNQQQNQ, NNQQQQN, QNNNQQQ,


 


QNNQNQQ, QNNQQNQ, QNNQQQN, QNQNNQQ, QNQQNNQ, QNQQQNN,


 


QNQNQNQ, QNQNQQN, QNQQNQN, QQNNNQQ, QQNNQNQ, QQNNQQN,


 


QQNQNNQ, QQNQNQN, QQNQQNN, QQQNNNQ, QQQNNQN, QQQNQNN,


 


QQQQQNN, NNQQQQQ, NQNQQQQ, NQQNQQQ, NQQQNQQ, NQQQQNQ,


 


NQQQQQN, QNNQQQQ, QNQNQQQ, QNQQNQQ, QNQQQNQ, QNQQQQN,


 


QQNNQQQ, QQNQNQQ, QQNQQNQ, QQNQQQN, QQQNNQQ, QQQNQNQ,


 


QQQNQQN, QQQQNNQ, QQQQNQN QQQQQQN, NQQQQQQ, QNQQQQQ,


 


QQNQQQQ, QQQNQQQ, QQQQNQQ, QQQQQNQ, QQD, DQQ, QDQ, QQQD,


 


DQQQ, QDQQ, QQDQ, QQQQD, DQQQQ, QDQQQ, QQDQQ, QQQDQ, QQQDD,


 


DDQQQ, DQDQQ, DQQDQ, DQQQD, QDDQQ, QDQDQ, QDQQD, QQDDQ,


 


QQDQD, QQQQQD, DQQQQQ, QDQQQQ, QQDQQQ, QQQDQQ, QQQQDQ,


 


QQQQDD, DDQQQQ, DQDQQQ, DQQDQQ, DQQQDQ, DQQQQD, QDDQQQ,


 


QDQDQQ, QDQQDQ, QDQQQD, QQDDQQ, QQDQDQ, QQDQQD, QQQDDQ,


 


QQQDQD, QQQQDDD, DDDQQQQ, DQDDQQQ, DQDQDQQ, DQDQQDQ,


 


DQDQQQD, DQQDDQQ, DQQDQDQ, DQQDQQD, DQQQDQD, DQQQDDQ,


 


DQQQQDD, DDQDQQQ, DDQQDQQ, DDQQQDQ, DDQQQQD, QDDDQQQ,


 


QDDQDQQ, QDDQQDQ, QDDQQQD, QDQDDQQ, QDQQDDQ, QDQQQDD,


 


QDQDQDQ, QDQDQQD, QDQQDQD, QQDDDQQ, QQDDQDQ, QQDDQQD,


 


QQDQDDQ, QQDQDQD, QQDQQDD, QQQDDDQ, QQQDDQD, QQQDQDD,


 


QQQQQDD, DDQQQQQ, DQDQQQQ, DQQDQQQ, DQQQDQQ, DQQQQDQ,


 


DQQQQQD, QDDQQQQ, QDQDQQQ, QDQQDQQ, QDQQQDQ, QDQQQQD,


 


QQDDQQQ, QQDQDQQ, QQDQQDQ, QQDQQQD, QQQDDQQ, QQQDQDQ,


 


QQQDQQD, QQQQDDQ, QQQQDQD QQQQQQD, DQQQQQQ, QDQQQQQ,


 


QQDQQQQ, QQQDQQQ, QQQQDQQ, and QQQQQDQ.
















TABLE 4







(SEQ ID NO: 2450)


        10         20         30         40         50         60


MFLQNLFLGF LAVVCANATP LGPASSLPQS FLLKCLEQVR KIQGDGAALQ EKLCATYKLC


 


        70         80         90        100        110        120


HPEELVLLGH SLGIPWAPLS SCPSQALQLA GCLSQLHSGL FLYQGLLQAL EGISPELGPT


 


       130        140        150        160        170        180


LDTLQLDVAD FATTIWQQME ELGMAPALQP TQGAMPAFAS AFQRRAGGVL VASHLQSFLE


 


       190        200        210        220        230        240


VSYRVLRHLA QPNNTNNTNN TNNTNNTNNT NNTNNTNNTN NTNNTNNTNN TNNTNNTNNT


 


       250        260        270        280        290        300


NNTNNTNNTN NTNNTNNTNN TNNTNNTNNT NNTNNTNNTN NTNNTNNTNN TNNTNNTNNT


 


       310        320        330        340        350         360


NNTNNTNNTN NTNNTNNTNN TNNTNNTNNT NNTNNTNNTN NTNNTNN*|.. ..........


 


(SEQ ID NO: 2451)


        10         20         30         40         50         60


atgttcttgc aaaatttatt ccttggcttt ttggccgttg tttgcgcaaa cgcgACTCCG


 


        70         80         90         100        110        120


CTGGGTCCAG CTAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTGCTTAGA GCAAGTGAGG


 


       130        140        150        160        170        180


AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC


 


       190        200        210        220        230        240


CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC


 


       250        260        270        280        290        300


AGCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT


 


       310        320        330        340        350        360


TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATCT CCCCCGAGTT GGGTCCCACC


 


       370        380        390        400        410        420


TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA


 


        430        440        450        460        470        480


|GAACTGGGAA TGGCCCCTGC CCTGCAGCCG ACCCAGGGTG CCATGCCGGC CTTCGCCTCT


 


       490        500        510        520        530        540


GCTTTCCAGC GCCGGGCAGG AGGGGTCCTA GTTGCCTCCC ATCTGCAGAG CTTCCTGGAG


 


       550        560        570        580        590        600


GTGTCGTACC GCGTTCTACG CCACCTTGCC CAGCCTAACA ACACCAACAA TACCAACAAT


 


       610        620        630        640        650        660


ACAAACAACA CCAACAATAC CAACAATACA AACAACACCA ACAATACCAA CAATACAAAC


 


       670        680        690        700        710        720


AACACCAACA ATACCAACAA TACAAACAAC ACCAACAATA CCAACAATAC AAACAACACC


 


       730        740        750        760        770        780


AACAATACCA ACAATACAAA CAACACCAAC AATACCAACA ATACAAACAA CACCAATAAT


 


       790        800        810        820        830        840


ACCAACAATA CAAACAACAC CAATAATACC AACAATACAA ACAACACCAA TAATACCAAC


 


       850        860        870        880        890        900


AATACAAACA ACACCAATAA TACCAACAAT ACAAACAACA CCAATAATAC CAACAATACA


 


       910        920        930        940        950        960


AACAACACCA ATAATACCAA CAATACAAAC AACACCAATA ATACCAACAA TACAAACAAC


 


       970        980        990       1000       1010       1020


ACCAATAATA CCAACAATAC AAACAACACC AATAATACCA ACAATACAAA CAACACCAAT


 


      1030       1040       1050       1060       1070       1080


AATACCAACA ATACAAACAA CTAG...... .......... .......... ..........
















TABLE 5







EPO


Homo sapiens erythropoietin (EPO), mRNA.


ACCESSION NM_000799


VERSION NM_000799.2 GI: 62240996


 


MGVHECPAWLWLLLSLLSLPLGLPVLGAPPRLICDSRVLERYLLEAKEAENITT


GCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRG


QALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPL


RTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR (SEQ ID NO: 2452)


 








1
cccggagccg gaccggggcc accgcgcccg ctctgctccg acaccgcgcc ccctggacag


 


61
ccgccctctc ctccaggccc gtggggctgg ccctgcaccg ccgagcttcc cgggatgagg


 


121
gcccccggtg tggtcacccg gcgcgcccca ggtcgctgag ggaccccggc caggcgcgga


 


181
gatgggggtg cacgaatgtc ctgcctggct gtggcttctc ctgtccctgc tgtcgctccc


 


241
tctgggcctc ccagtcctgg gcgccccacc acgcctcatc tgtgacagcc gagtcctgga


 


301
gaggtacctc ttggaggcca aggaggccga gaatatcacg acgggctgtg ctgaacactg


 


361
cagcttgaat gagaatatca ctgtcccaga caccaaagtt aatttctatg cctggaagag


 


421
gatggaggtc gggcagcagg ccgtagaagt ctggcagggc ctggccctgc tgtcggaagc


 


481
tgtcctgcgg ggccaggccc tgttggtcaa ctcttcccag ccgtgggagc ccctgcagct


 


541
gcatgtggat aaagccgtca gtggccttcg cagcctcacc actctgcttc gggctctggg


 


601
agcccagaag gaagccatct cccctccaga tgcggcctca gctgctccac tccgaacaat


 


661
cactgctgac actttccgca aactcttccg agtctactcc aatttcctcc ggggaaagct


 


721
gaagctgtac acaggggagg cctgcaggac aggggacaga tgaccaggtg tgtccacctg


 


781
ggcatatcca ccacctccct caccaacatt gcttgtgcca caccctcccc cgccactcct


 


841
gaaccccgtc gaggggctct cagctcagcg ccagcctgtc ccatggacac tccagtgcca


 


901
gcaatgacat ctcaggggcc agaggaactg tccagagagc aactctgaga tctaaggatg


 


961
tcacagggcc aacttgaggg cccagagcag gaagcattca gagagcagct ttaaactcag


 


1021
ggacagagcc atgctgggaa gacgcctgag ctcactcggc accctgcaaa atttgatgcc


 


1081
aggacacgct ttggaggcga tttacctgtt ttcgcaccta ccatcaggga caggatgacc


 


1141
tggagaactt aggtggcaag ctgtgacttc tccaggtctc acgggcatgg gcactccctt


 


1201
ggtggcaaga gcccccttga caccggggtg gtgggaacca tgaagacagg atgggggctg


 


1261
gcctctggct ctcatggggt ccaagttttg tgtattcttc aacctcattg acaagaactg


 


1321
aaaccaccaa aaaaaaaaaa (SEQ ID NO: 2453)


 







MCSF


Homo sapiens colony stimulating factor 1 (macrophage) (CSF1),


transcript variant 4, mRNA.


ACCESSION NM_172212


VERSION NM_172212.1 GI: 27262666


 


MTAPGAAGRCPPTTWLGSLLLLVCLLASRSITEEVSEYCSHMIGSGHLQSLQR


LIDSQMETSCQITFEFVDQEQLKDPVCYLKKAFLLVQDIMEDTMRFRDNTPNA


IAIVQLQELSLRLKSCFTKDYEEHDKACVRTFYETPLQLLEKVKNVFNETKNLL


DKDWNIFSKNCNNSFAECSSQDVVTKPDCNCLYPKAIPSSDPASVSPHQPLAP


SMAPVAGLTWEDSEGTEGSSLLPGEQPLHTVDPGSAKQRPPRSTCQSFEPPET


PVVKDSTIGGSPQPRPSVGAFNPGMEDILDSAMGTNWVPEEASGEASEIPVPQ


GTELSPSRPGGGSMQTEPARPSNFLSASSPLPASAKGQQPADVTGTALPRVGP


VRPTGQDWNHTPQKTDHPSALLRDPPEPGSPRISSLRPQGLSNPSTLSAQPQLS


RSHSSGSVLPLGELEGRRSTRDRRSPAEPEGGPASEGAARPLPRFNSVPLTDTG


HERQSEGSSSPQLQESVFHLLVPSVILVLLAVGGLLFYRWRRRSHQEPQRADS


PLEQPEGSPLTQDDRQVELPV (SEQ ID NO: 2454)


 








1
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc


 


61
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc


 


121
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca


 


181
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc


 


241
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag


 


301
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt


 


361
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat


 


421
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg


 


481
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg


 


541
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact


 


601
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag


 


661
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa


 


721
tgctccagcc aagatgtggt gaccaagcct gattgcaact gcctgtaccc caaagccatc


 


781
cctagcagtg acccggcctc tgtctcccct catcagcccc tcgccccctc catggcccct


 


841
gtggctggct tgacctggga ggactctgag ggaactgagg gcagctccct cttgcctggt


 


901
gagcagcccc tgcacacagt ggatccaggc agtgccaagc agcggccacc caggagcacc


 


961
tgccagagct ttgagccgcc agagacccca gttgtcaagg acagcaccat cggtggctca


 


1021
ccacagcctc gcccctctgt cggggccttc aaccccggga tggaggatat tcttgactct


 


1081
gcaatgggca ctaattgggt cccagaagaa gcctctggag aggccagtga gattcccgta


 


1141
ccccaaggga cagagctttc cccctccagg ccaggagggg gcagcatgca gacagagccc


 


1201
gccagaccca gcaacttcct ctcagcatct tctccactcc ctgcatcagc aaagggccaa


 


1261
cagccggcag atgtaactgg tacagccttg cccagggtgg gccccgtgag gcccactggc


 


1321
caggactgga atcacacccc ccagaagaca gaccatccat ctgccctgct cagagacccc


 


1381
ccggagccag gctctcccag gatctcatca ctgcgccccc agggcctcag caacccctcc


 


1441
accctctctg ctcagccaca gctttccaga agccactcct cgggcagcgt gctgcccctt


 


1501
ggggagctgg agggcaggag gagcaccagg gatcggagga gccccgcaga gccagaagga


 


1561
ggaccagcaa gtgaaggggc agccaggccc ctgccccgtt ttaactccgt tcctttgact


 


1621
gacacaggcc atgagaggca gtccgaggga tcctccagcc cgcagctcca ggagtctgtc


 


1681
ttccacctgc tggtgcccag tgtcatcctg gtcttgctgg ccgtcggagg cctcttgttc


 


1741
tacaggtgga ggcggcggag ccatcaagag cctcagagag cggattctcc cttggagcaa


 


1801
ccagagggca gccccctgac tcaggatgac agacaggtgg aactgccagt gtagagggaa


 


1861
ttctaagacc cctcaccatc ctggacacac tcgtttgtca atgtccctct gaaaatgtga


 


1921
cgcccagccc cggacacagt actccagatg ttgtctgacc agctcagaga gagtacagtg


 


1981
ggactgttac cttccttgat atggacagta ttcttctatt tgtgcagatt aagattgcat


 


2041
tagttttttt cttaacaact gcatcatact gttgtcatat gttgagcctg tggttctata


 


2101
aaacccctag ttccatttcc cataaacttc tgtcaagcca gaccatctct accctgtact


 


2161
tggacaactt aactttttta accaaagtgc agtttatgtt cacctttgtt aaagccacct


 


2221
ttgtggtttc tgcccatcac ctgaacctac tgaagttgtg tgaaatccta attctgtcat


 


2281
ctccgtagcc ctcccagttg tgcctcctgc acattgatga gtgcctgctg ttgtctttgc


 


2341
ccatgttgtt gatgtagctg tgaccctatt gttcctcacc cctgcccccc gccaacccca


 


2401
gctggcccac ctcttccccc tcccacccaa gcccacagcc agcccatcag gaagccttcc


 


2461
tggcttctcc acaaccttct gactgtcttt tcagtcatgc cccctgctct tttgtatttg


 


2521
gctaatagta tatcaatttg cactt (SEQ ID NO: 2455)


 







Homo sapiens colony stimulating factor 1 (macrophage) (CSF1),


transcript variant 3, mRNA.


ACCESSION NM_172211


VERSION NM_172211.1 GI: 27262664


 


MTAPGAAGRCPPTTWLGSLLLLVCLLASRSITEEVSEYCSHMIGSGHLQSLQR


LIDSQMETSCQITFEFVDQEQLKDPVCYLKKAFLLVQDIMEDTMRFRDNTPNA


IAIVQLQELSLRLKSCFTKDYEEHDKACVRTFYETPLQLLEKVKNVFNETKNLL


DKDWNIFSKNCNNSFAECSSQGHERQSEGSSSPQLQESVFHLLVPSVILVLLAV


GGLLFYRWRRRSHQEPQRADSPLEQPEGSPLTQDDRQVELPV (SEQ ID NO: 2456)


 








1
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc


 


61
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc


 


121
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca


 


181
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc


 


241
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag


 


301
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt


 


361
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat


 


421
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg


 


481
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg


 


541
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact


 


601
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag


 


661
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa


 


721
tgctccagcc aaggccatga gaggcagtcc gagggatcct ccagcccgca gctccaggag


 


781
tctgtcttcc acctgctggt gcccagtgtc atcctggtct tgctggccgt cggaggcctc


 


841
ttgttctaca ggtggaggcg gcggagccat caagagcctc agagagcgga ttctcccttg


 


901
gagcaaccag agggcagccc cctgactcag gatgacagac aggtggaact gccagtgtag


 


961
agggaattct aagctggacg cacagaacag tctctccgtg ggaggagaca ttatggggcg


 


1021
tccaccacca cccctccctg gccatcctcc tggaatgtgg tctgccctcc accagagctc


 


1081
ctgcctgcca ggactggacc agagcagcca ggctggggcc cctctgtctc aacccgcaga


 


1141
cccttgactg aatgagagag gccagaggat gctccccatg ctgccactat ttattgtgag


 


1201
ccctggaggc tcccatgtgc ttgaggaagg ctggtgagcc cggctcagga ccctcttccc


 


1261
tcaggggctg caccctcctc tcactccctt ccatgccgga acccaggcca gggacccacc


 


1321
ggcctgtggt ttgtgggaaa gcagggtgga cgctgaggag tgaaagaacc ctgcacccag


 


1381
agggcctgcc tggtgccaag gtatcccagc ctggacaggc atggacctgt ctccagagag


 


1441
aggagcctga agttcgtggg gcgggacagc gtcggcctga tttcccgtaa aggtgtgcag


 


1501
cctgagagac gggaagagga ggcctctgga cctgctggtc tgcactgaca gcctgaaggg


 


1561
tctacaccct cggctcacct aagtgccctg tgctggttgc caggcgcaga ggggaggcca


 


1621
gccctgccct caggacctgc ctgacctgcc agtgatgcca agagggggat caagcactgg


 


1681
cctctgcccc tcctccttcc agcacctgcc agagcttctc caggaggcca agcagaggct


 


1741
cccctcatga aggaagccat tgcactgtga acactgtacc tgcctgctga acagcctgcc


 


1801
cccgtccatc catgagccag catccgtccg tcctccactc tccagcctct cccca (SEQ ID NO: 2457)


 







Homo sapiens colony stimulating factor 1 (macrophage) (CSF1),


transcript variant 2, mRNA.


ACCESSION NM_172210


VERSION NM_172210.1 GI: 27262662


 


MTAPGAAGRCPPTTWLGSLLLLVCLLASRSITEEVSEYCSHMIGSGHLQSLQR


LIDSQMETSCQITFEFVDQEQLKDPVCYLKKAFLLVQDIMEDTMRFRDNTPNA


IAIVQLQELSLRLKSCFTKDYEEHDKACVRTFYETPLQLLEKVKNVFNETKNLL


DKDWNIFSKNCNNSFAECSSQDVVTKPDCNCLYPKAIPSSDPASVSPHQPLAP


SMAPVAGLTWEDSEGTEGSSLLPGEQPLHTVDPGSAKQRPPRSTCQSFEPPET


PVVKDSTIGGSPQPRPSVGAFNPGMEDILDSAMGTNWVPEEASGEASEIPVPQ


GTELSPSRPGGGSMQTEPARPSNFLSASSPLPASAKGQQPADVTGHERQSEGS


SSPQLQESVFHLLVPSVILVLLAVGGLLFYRWRRRSHQEPQRADSPLEQPEGSP


LTQDDRQVELPV (SEQ ID NO: 2458)


 








1
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc


 


61
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc


 


121
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca


 


181
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc


 


241
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag


 


301
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt


 


361
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat


 


421
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg


 


481
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg


 


541
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact


 


601
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag


 


661
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa


 


721
tgctccagcc aagatgtggt gaccaagcct gattgcaact gcctgtaccc caaagccatc


 


781
cctagcagtg acccggcctc tgtctcccct catcagcccc tcgccccctc catggcccct


 


841
gtggctggct tgacctggga ggactctgag ggaactgagg gcagctccct cttgcctggt


 


901
gagcagcccc tgcacacagt ggatccaggc agtgccaagc agcggccacc caggagcacc


 


961
tgccagagct ttgagccgcc agagacccca gttgtcaagg acagcaccat cggtggctca


 


1021
ccacagcctc gcccctctgt cggggccttc aaccccggga tggaggatat tcttgactct


 


1081
gcaatgggca ctaattgggt cccagaagaa gcctctggag aggccagtga gattcccgta


 


1141
ccccaaggga cagagctttc cccctccagg ccaggagggg gcagcatgca gacagagccc


 


1201
gccagaccca gcaacttcct ctcagcatct tctccactcc ctgcatcagc aaagggccaa


 


1261
cagccggcag atgtaactgg ccatgagagg cagtccgagg gatcctccag cccgcagctc


 


1321
caggagtctg tcttccacct gctggtgccc agtgtcatcc tggtcttgct ggccgtcgga


 


1381
ggcctcttgt tctacaggtg gaggcggcgg agccatcaag agcctcagag agcggattct


 


1441
cccttggagc aaccagaggg cagccccctg actcaggatg acagacaggt ggaactgcca


 


1501
gtgtagaggg aattctaag (SEQ ID NO: 2459)


 







Homo sapiens colony stimulating factor 1 (macrophage) (CSF1),


transcript variant 1, mRNA.


ACCESSION NM_000757


VERSION NM_000757.3 GI: 27262660


 


MTAPGAAGRCPPTTWLGSLLLLVCLLASRSITEEVSEYCSHMIGSGHLQSLQR


LIDSQMETSCQITFEFVDQEQLKDPVCYLKKAFLLVQDIMEDTMRFRDNTPNA


IAIVQLQELSLRLKSCFTKDYEEHDKACVRTFYETPLQLLEKVKNFVFNETKNLL


DKDWNIFSKNCNNSFAECSSQDVVTKPDCNCLYPKAIPSSDPASVSPHQPLAP


SMAPVAGLTWEDSEGTEGSSLLPGEQPLHTVDPGSAKQRPPRSTCQSFEPPET


PVVKDSTIGGSPQPRPSVGAFNPGMEDILDSAMGTNWVPEEASGEASEIPVPQ


GTELSPSRPGGGSMQTEPARPSNFLSASSPLPASAKGQQPADVTGTALPRVGP


VRPTGQDWNHTPQKTDHPSALLRDPPEPGSPRISSLRPQGLSNPSTLSAQPQLS


RSHSSGSVLPLGELEGRRSTRDRRSPAEPEGGPASEGAARPLPRFNSVPLTDTG


HERQSEGSSSPQLQESVFHLLVPSVILVLLAVGGLLFYRWRRRSHQEPQRADS


PLEQPEGSPLTQDDRQVELPV (SEQ ID NO: 2460)


 








1
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc


 


61
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc


 


121
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca


 


181
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc


 


241
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag


 


301
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt


 


361
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat


 


421
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg


 


481
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg


 


541
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact


 


601
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag


 


661
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa


 


721
tgctccagcc aagatgtggt gaccaagcct gattgcaact gcctgtaccc caaagccatc


 


781
cctagcagtg acccggcctc tgtctcccct catcagcccc tcgccccctc catggcccct


 


841
gtggctggct tgacctggga ggactctgag ggaactgagg gcagctccct cttgcctggt


 


901
gagcagcccc tgcacacagt ggatccaggc agtgccaagc agcggccacc caggagcacc


 


961
tgccagagct ttgagccgcc agagacccca gttgtcaagg acagcaccat cggtggctca


 


1021
ccacagcctc gcccctctgt cggggccttc aaccccggga tggaggatat tcttgactct


 


1081
gcaatgggca ctaattgggt cccagaagaa gcctctggag aggccagtga gattcccgta


 


1141
ccccaaggga cagagctttc cccctccagg ccaggagggg gcagcatgca gacagagccc


 


1201
gccagaccca gcaacttcct ctcagcatct tctccactcc ctgcatcagc aaagggccaa


 


1261
cagccggcag atgtaactgg tacagccttg cccagggtgg gccccgtgag gcccactggc


 


1321
caggactgga atcacacccc ccagaagaca gaccatccat ctgccctgct cagagacccc


 


1381
ccggagccag gctctcccag gatctcatca ctgcgccccc agggcctcag caacccctcc


 


1441
accctctctg ctcagccaca gctttccaga agccactcct cgggcagcgt gctgcccctt


 


1501
ggggagctgg agggcaggag gagcaccagg gatcggagga gccccgcaga gccagaagga


 


1561
ggaccagcaa gtgaaggggc agccaggccc ctgccccgtt ttaactccgt tcctttgact


 


1621
gacacaggcc atgagaggca gtccgaggga tcctccagcc cgcagctcca ggagtctgtc


 


1681
ttccacctgc tggtgcccag tgtcatcctg gtcttgctgg ccgtcggagg cctcttgttc


 


1741
tacaggtgga ggcggcggag ccatcaagag cctcagagag cggattctcc cttggagcaa


 


1801
ccagagggca gccccctgac tcaggatgac agacaggtgg aactgccagt gtagagggaa


 


1861
ttctaagctg gacgcacaga acagtctctc cgtgggagga gacattatgg ggcgtccacc


 


1921
accacccctc cctggccatc ctcctggaat gtggtctgcc ctccaccaga gctcctgcct


 


1981
gccaggactg gaccagagca gccaggctgg ggcccctctg tctcaacccg cagacccttg


 


2041
actgaatgag agaggccaga ggatgctccc catgctgcca ctatttattg tgagccctgg


 


2101
aggctcccat gtgcttgagg aaggctggtg agcccggctc aggaccctct tccctcaggg


 


2161
gctgcaccct cctctcactc ccttccatgc cggaacccag gccagggacc caccggcctg


 


2221
tggtttgtgg gaaagcaggg tggacgctga ggagtgaaag aaccctgcac ccagagggcc


 


2281
tgcctggtgc caaggtatcc cagcctggac aggcatggac ctgtctccag agagaggagc


 


2341
ctgaagttcg tggggcggga cagcgtcggc ctgatttccc gtaaaggtgt gcagcctgag


 


2401
agacgggaag aggaggcctc tggacctgct ggtctgcact gacagcctga agggtctaca


 


2461
ccctcggctc acctaagtgc cctgtgctgg ttgccaggcg cagaggggag gccagccctg


 


2521
ccctcaggac ctgcctgacc tgccagtgat gccaagaggg ggatcaagca ctggcctctg


 


2581
cccctcctcc ttccagcacc tgccagagct tctccaggag gccaagcaga ggctcccctc


 


2641
atgaaggaag ccattgcact gtgaacactg tacctgcctg ctgaacagcc tgcccccgtc


 


2701
catccatgag ccagcatccg tccgtcctcc actctccagc ctctcccca (SEQ ID NO: 2461)


 







GM-CSF


Homo sapiens colony stimulating factor 2 (granulocyte-macrophage)


(CSF2), mRNA.


ACCESSION NM_000758


VERSION NM_000758.2 GI: 27437029


 


MWLQSLLLLGTVACSISAPARSPSPSTQPWEHVNAIQEARRLLN


LSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLT


KLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLL


VIPFDCWEPVQE (SEQ ID NO: 2462)


 








1
acacagagag aaaggctaaa gttctctgga ggatgtggct gcagagcctg ctgctcttgg


 


61
gcactgtggc ctgcagcatc tctgcacccg cccgctcgcc cagccccagc acgcagccct


 


121
gggagcatgt gaatgccatc caggaggccc ggcgtctcct gaacctgagt agagacactg


 


181
ctgctgagat gaatgaaaca gtagaagtca tctcagaaat gtttgacctc caggagccga


 


241
cctgcctaca gacccgcctg gagctgtaca agcagggcct gcggggcagc ctcaccaagc


 


301
tcaagggccc cttgaccatg atggccagcc actacaagca gcactgccct ccaaccccgg


 


361
aaacttcctg tgcaacccag attatcacct ttgaaagttt caaagagaac ctgaaggact


 


421
ttctgcttgt catccccttt gactgctggg agccagtcca ggagtgagac cggccagatg


 


481
aggctggcca agccggggag ctgctctctc atgaaacaag agctagaaac tcaggatggt


 


541
catcttggag ggaccaaggg gtgggccaca gccatggtgg gagtggcctg gacctgccct


 


601
gggccacact gaccctgata caggcatggc agaagaatgg gaatatttta tactgacaga


 


661
aatcagtaat atttatatat ttatattttt aaaatattta tttatttatt tatttaagtt


 


721
catattccat atttattcaa gatgttttac cgtaataatt attattaaaa atatgcttct


 


781
a (SEQ ID NO: 2463)


 







TNF-ALPHA TYPE II RECEPTOR


Homo sapiens tumor necrosis factor (TNF superfamily, member 2)


(TNF), mRNA.


ACCESSION NM_000594


VERSION NM_000594.2 GI: 25952110


 


MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFG


VIGPQREEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNR


RANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAV


SYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRP


DYLDFAESGQVYFGIIAL (SEQ ID NO: 2464)


 








1
ctccctcagc aaggacagca gaggaccagc taagagggag agaagcaact acagaccccc


 


61
cctgaaaaca accctcagac gccacatccc ctgacaagct gccaggcagg ttctcttcct


 


121
ctcacatact gacccacggc tccaccctct ctcccctgga aaggacacca tgagcactga


 


181
aagcatgatc cgggacgtgg agctggccga ggaggcgctc cccaagaaga caggggggcc


 


241
ccagggctcc aggcggtgct tgttcctcag cctcttctcc ttcctgatcg tggcaggcgc


 


301
caccacgctc ttctgcctgc tgcactttgg agtgatcggc ccccagaggg aagagttccc


 


361
cagggacctc tctctaatca gccctctggc ccaggcagtc agatcatctt ctcgaacccc


 


421
gagtgacaag cctgtagccc atgttgtagc aaaccctcaa gctgaggggc agctccagtg


 


481
gctgaaccgc cgggccaatg ccctcctggc caatggcgtg gagctgagag ataaccagct


 


541
ggtggtgcca tcagagggcc tgtacctcat ctactcccag gtcctcttca agggccaagg


 


601
ctgcccctcc acccatgtgc tcctcaccca caccatcagc cgcatcgccg tctcctacca


 


661
gaccaaggtc aacctcctct ctgccatcaa gagcccctgc cagagggaga ccccagaggg


 


721
ggctgaggcc aagccctggt atgagcccat ctatctggga ggggtcttcc agctggagaa


 


781
gggtgaccga ctcagcgctg agatcaatcg gcccgactat ctcgactttg ccgagtctgg


 


841
gcaggtctac tttgggatca ttgccctgtg aggaggacga acatccaacc ttcccaaacg


 


901
cctcccctgc cccaatccct ttattacccc ctccttcaga caccctcaac ctcttctggc


 


961
tcaaaaagag aattgggggc ttagggtcgg aacccaagct tagaacttta agcaacaaga


 


1021
ccaccacttc gaaacctggg attcaggaat gtgtggcctg cacagtgaag tgctggcaac


 


1081
cactaagaat tcaaactggg gcctccagaa ctcactgggg cctacagctt tgatccctga


 


1141
catctggaat ctggagacca gggagccttt ggttctggcc agaatgctgc aggacttgag


 


1201
aagacctcac ctagaaattg acacaagtgg accttaggcc ttcctctctc cagatgtttc


 


1261
cagacttcct tgagacacgg agcccagccc tccccatgga gccagctccc tctatttatg


 


1321
tttgcacttg tgattattta ttatttattt attatttatt tatttacaga tgaatgtatt


 


1381
tatttgggag accggggtat cctgggggac ccaatgtagg agctgccttg gctcagacat


 


1441
gttttccgtg aaaacggagc tgaacaatag gctgttccca tgtagccccc tggcctctgt


 


1501
gccttctttt gattatgttt tttaaaatat ttatctgatt aagttgtcta aacaatgctg


 


1561
atttggtgac caactgtcac tcattgctga gcctctgctc cccaggggag ttgtgtctgt


 


1621
aatcgcccta ctattcagtg gcgagaaata aagtttgctt agaaaagaa (SEQ ID NO: 2465)


 







DEFINITION Homo sapiens tumor necrosis factor receptor superfamily,


member 1A


(TNFRSF1A), mRNA.


ACCESSION NM_001065


VERSION NM_001065.2 GI: 23312372


 


MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQN


NSICCTKCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRK


EMGQVEISSCTVDRDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQ


EKQNTVCTCHAGFFLRENECVSCSNCKKSLECTKLCLPQIENVKGTEDSGTTV


LLPLVIFFGLCLLSLLFIGLMYRYQRWKSKLYSIVCGKSTPEKEGELEGTTTKPL


APNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYTPGDCPNFAAPRREVAPPYQGAD


PILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLYAVVENVPPLRWKEFV


RRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLELLGRVLRD


MDLLGCLEDIEEALCGPAALPPAPSLLR (SEQ ID NO: 2466)


 








1
gctgttgcaa cactgcctca ctcttcccct cccaccttct ctcccctcct ctctgcttta


 


61
attttctcag aattctctgg actgaggctc cagttctggc ctttggggtt caagatcact


 


121
gggaccaggc cgtgatctct atgcccgagt ctcaaccctc aactgtcacc ccaaggcact


 


181
tgggacgtcc tggacagacc gagtcccggg aagccccagc actgccgctg ccacactgcc


 


241
ctgagcccaa atgggggagt gagaggccat agctgtctgg catgggcctc tccaccgtgc


 


301
ctgacctgct gctgccactg gtgctcctgg agctgttggt gggaatatac ccctcagggg


 


361
ttattggact ggtccctcac ctaggggaca gggagaagag agatagtgtg tgtccccaag


 


421
gaaaatatat ccaccctcaa aataattcga tttgctgtac caagtgccac aaaggaacct


 


481
acttgtacaa tgactgtcca ggcccggggc aggatacgga ctgcagggag tgtgagagcg


 


541
gctccttcac cgcttcagaa aaccacctca gacactgcct cagctgctcc aaatgccgaa


 


601
aggaaatggg tcaggtggag atctcttctt gcacagtgga ccgggacacc gtgtgtggct


 


661
gcaggaagaa ccagtaccgg cattattgga gtgaaaacct tttccagtgc ttcaattgca


 


721
gcctctgcct caatgggacc gtgcacctct cctgccagga gaaacagaac accgtgtgca


 


781
cctgccatgc aggtttcttt ctaagagaaa acgagtgtgt ctcctgtagt aactgtaaga


 


841
aaagcctgga gtgcacgaag ttgtgcctac cccagattga gaatgttaag ggcactgagg


 


901
actcaggcac cacagtgctg ttgcccctgg tcattttctt tggtctttgc cttttatccc


 


961
tcctcttcat tggtttaatg tatcgctacc aacggtggaa gtccaagctc tactccattg


 


1021
tttgtgggaa atcgacacct gaaaaagagg gggagcttga aggaactact actaagcccc


 


1081
tggccccaaa cccaagcttc agtcccactc caggcttcac ccccaccctg ggcttcagtc


 


1141
ccgtgcccag ttccaccttc acctccagct ccacctatac ccccggtgac tgtcccaact


 


1201
ttgcggctcc ccgcagagag gtggcaccac cctatcaggg ggctgacccc atccttgcga


 


1261
cagccctcgc ctccgacccc atccccaacc cccttcagaa gtgggaggac agcgcccaca


 


1321
agccacagag cctagacact gatgaccccg cgacgctgta cgccgtggtg gagaacgtgc


 


1381
ccccgttgcg ctggaaggaa ttcgtgcggc gcctagggct gagcgaccac gagatcgatc


 


1441
ggctggagct gcagaacggg cgctgcctgc gcgaggcgca atacagcatg ctggcgacct


 


1501
ggaggcggcg cacgccgcgg cgcgaggcca cgctggagct gctgggacgc gtgctccgcg


 


1561
acatggacct gctgggctgc ctggaggaca tcgaggaggc gctttgcggc cccgccgccc


 


1621
tcccgcccgc gcccagtctt ctcagatgag gctgcgcccc tgcgggcagc tctaaggacc


 


1681
gtcctgcgag atcgccttcc aaccccactt ttttctggaa aggaggggtc ctgcaggggc


 


1741
aagcaggagc tagcagccgc ctacttggtg ctaacccctc gatgtacata gcttttctca


 


1801
gctgcctgcg cgccgccgac agtcagcgct gtgcgcgcgg agagaggtgc gccgtgggct


 


1861
caagagcctg agtgggtggt ttgcgaggat gagggacgct atgcctcatg cccgttttgg


 


1921
gtgtcctcac cagcaaggct gctcgggggc ccctggttcg tccctgagcc tttttcacag


 


1981
tgcataagca gttttttttg tttttgtttt gttttgtttt gtttttaaat caatcatgtt


 


2041
acactaatag aaacttggca ctcctgtgcc ctctgcctgg acaagcacat agcaagctga


 


2101
actgtcctaa ggcaggggcg agcacggaac aatggggcct tcagctggag ctgtggactt


 


2161
ttgtacatac actaaaattc tgaagttaaa gctctgctct tggaaaaaaa aaaaaaaaaa


 


2221
aaaaaaaaaa aaaaaa (SEQ ID NO: 2467)


 







BETA INTERFERON


Homo sapiens interferon, beta 1, fibroblast (IFNB1), mRNA.


ACCESSION NM_002176


VERSION NM_002176.2 GI: 50593016


 


MTNKCLLQIALLLCFSTTALSMSYNLLGFLQRSSNFQCQKLLWQLNGRLEYCL


KDRMNFDIPEEIKQLQQFQKEDAALTIYEMLQNIFAIFRQDSSSTGWNETIVEN


LLANVYHQINHLKTVLEEKLEKEDFTRGKLMSSLHLKRYYGRILHYLKAKEY


SHCAWTIVRVEILRNFYFINRLTGYLRN (SEQ ID NO: 2468)


 








1
acattctaac tgcaaccttt cgaagccttt gctctggcac aacaggtagt aggcgacact


 


61
gttcgtgttg tcaacatgac caacaagtgt ctcctccaaa ttgctctcct gttgtgcttc


 


121
tccactacag ctctttccat gagctacaac ttgcttggat tcctacaaag aagcagcaat


 


181
tttcagtgtc agaagctcct gtggcaattg aatgggaggc ttgaatactg cctcaaggac


 


241
aggatgaact ttgacatccc tgaggagatt aagcagctgc agcagttcca gaaggaggac


 


301
gccgcattga ccatctatga gatgctccag aacatctttg ctattttcag acaagattca


 


361
tctagcactg gctggaatga gactattgtt gagaacctcc tggctaatgt ctatcatcag


 


421
ataaaccatc tgaagacagt cctggaagaa aaactggaga aagaagattt caccagggga


 


481
aaactcatga gcagtctgca cctgaaaaga tattatggga ggattctgca ttacctgaag


 


541
gccaaggagt acagtcactg tgcctggacc atagtcagag tggaaatcct aaggaacttt


 


601
tacttcatta acagacttac aggttacctc cgaaactgaa gatctcctag cctgtgcctc


 


661
tgggactgga caattgcttc aagcattctt caaccagcag atgctgttta agtgactgat


 


721
ggctaatgta ctgcatatga aaggacacta gaagattttg aaatttttat taaattatga


 


781
gttattttta tttatttaaa ttttattttg gaaaataaat tatttttggt gcaaaagtca (SEQ ID NO: 2469)


 







GAMMA INTERFERON


Homo sapiens interferon, gamma (IFNG), mRNA.


ACCESSION NM_000619


VERSION NM_000619.2 GI: 56786137


 


MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLF


LGILKNWKEESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFN


SNKKKRDDFEKLTNYSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQML


FRGRRASQ (SEQ ID NO: 2470)


 








1
cacattgttc tgatcatctg aagatcagct attagaagag aaagatcagt taagtccttt


 


61
ggacctgatc agcttgatac aagaactact gatttcaact tctttggctt aattctctcg


 


121
gaaacgatga aatatacaag ttatatcttg gcttttcagc tctgcatcgt tttgggttct


 


181
cttggctgtt actgccagga cccatatgta aaagaagcag aaaaccttaa gaaatatttt


 


241
aatgcaggtc attcagatgt agcggataat ggaactcttt tcttaggcat tttgaagaat


 


301
tggaaagagg agagtgacag aaaaataatg cagagccaaa ttgtctcctt ttacttcaaa


 


361
ctttttaaaa actttaaaga tgaccagagc atccaaaaga gtgtggagac catcaaggaa


 


421
gacatgaatg tcaagttttt caatagcaac aaaaagaaac gagatgactt cgaaaagctg


 


481
actaattatt cggtaactga cttgaatgtc caacgcaaag caatacatga actcatccaa


 


541
gtgatggctg aactgtcgcc agcagctaaa acagggaagc gaaaaaggag tcagatgctg


 


601
tttcgaggtc gaagagcatc ccagtaatgg ttgtcctgcc tgcaatattt gaattttaaa


 


661
tctaaatcta tttattaata tttaacatta tttatatggg gaatatattt ttagactcat


 


721
caatcaaata agtatttata atagcaactt ttgtgtaatg aaaatgaata tctattaata


 


781
tatgtattat ttataattcc tatatcctgt gactgtctca cttaatcctt tgttttctga


 


841
ctaattaggc aaggctatgt gattacaagg ctttatctca ggggccaact aggcagccaa


 


901
cctaagcaag atcccatggg ttgtgtgttt atttcacttg atgatacaat gaacacttat


 


961
aagtgaagtg atactatcca gttactgccg gtttgaaaat atgcctgcaa tctgagccag


 


1021
tgctttaatg gcatgtcaga cagaacttga atgtgtcagg tgaccctgat gaaaacatag


 


1081
catctcagga gatttcatgc ctggtgcttc caaatattgt tgacaactgt gactgtaccc


 


1141
aaatggaaag taactcattt gttaaaatta tcaatatcta atatatatga ataaagtgta


 


1201
agttcacaac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa (SEQ ID NO: 2471)


 







HUMAN GROWTH HORMONE


Human growth hormone (somatotropin, GH1) gene, complete cds.


ACCESSION J00148 K00612


VERSION J00148.1 GI: 183145


 


MATGSRTSLLLAFGLLCLPWLQEGSAFPTIPLSRLFDNASLRAHRLHQLAFDTY


QEFNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFAN


SLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHN


DDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF (SEQ ID NO: 2472)


 








1
agggcaccca cgtgaccctt aaagagagga caagttgggt ggtattttct ggctgacact


 


61
ctgtgcacaa ccctcacaac actggttgac ggtgggaagg gaaagatgac aagccagggg


 


121
catgatccca gcatgtgtgg gaggagcttc taaattatcc attagcacaa gcccgtcagt


 


181
ggccccatgc ataaatgtac acagaaacag gtgggggcaa cagtgggaga gaaggggcca


 


241
gggtataaaa agggcccaca agagaccggc tcaaggatcc caaggcccaa ctccccgaac


 


301
cactcagggt cctgtggacg ctcacctagc tgcaatggct acaggtaagc gcccctaaaa


 


361
tccctttggg cacaatgtgt cctgagggga gaggcagcga cctgtagatg ggacgggggc


 


421
actaaccctc aggtttgggg cttctgaatg agtatcgcca tgtaagccca gtatggccaa


 


481
tctcagaaag ctcctggtcc ctggagggat ggagagagaa aaacaaacag ctcctggagc


 


541
agggagagtg ctggcctctt gctctccggc tccctctgtt gccctctggt ttctccccag


 


601
gctcccggac gtccctgctc ctggcttttg gcctgctctg cctgccctgg cttcaagagg


 


661
gcagtgcctt cccaaccatt cccttatcca ggctttttga caacgctagt ctccgcgccc


 


721
atcgtctgca ccagctggcc tttgacacct accaggagtt tgtaagctct tggggaatgg


 


781
gtgcgcatca ggggtggcag gaaggggtga ctttcccccg ctgggaaata agaggaggag


 


841
actaaggagc tcagggtttt tcccgaagcg aaaatgcagg cagatgagca cacgctgagt


 


901
gaggttccca gaaaagtaac aatgggagct ggtctccagc gtagaccttg gtgggcggtc


 


961
cttctcctag gaagaagcct atatcccaaa ggaacagaag tattcattcc tgcagaaccc


 


1021
ccagacctcc ctctgtttct cagagtctat tccgacaccc tccaacaggg aggaaacaca


 


1081
acagaaatcc gtgagtggat gccttgaccc caggcgggga tgggggagac ctgtagtcag


 


1141
agcccccggg cagcacaggc caatgcccgt ccttcccctg cagaacctag agctgctccg


 


1201
catctccctg ctgctcatcc agtcgtggct ggagcccgtg cagttcctca ggagtgtctt


 


1261
cgccaacagc ctggtgtacg gcgcctctga cagcaacgtc tatgacctcc taaaggacct


 


1321
agaggaaggc atccaaacgc tgatgggggt gggggtggcg ctaggggtcc ccaatcttgg


 


1381
agccccactg actttgagag ctgtgttaga gaaacactgc tgccctcttt ttagcagtcc


 


1441
aggccctgac ccaagagaac tcaccttatt cttcatttcc cctcgtgaat cctctagcct


 


1501
ttctctacac cctgaagggg agggaggaaa atgaatgaat gagaaaggga gggagcagta


 


1561
cccaagcgct tggcctctcc ttctcttcct tcactttgca gaggctggaa gatggcagcc


 


1621
cccggactgg gcagatcttc aagcagacct acagcaagtt cgacacaaac tcacacaacg


 


1681
atgacgcact actcaagaac tacgggctgc tctactgctt caggaaggac atggacaagg


 


1741
tcgagacatt cctgcgcatc gtgcagtgcc gctctgtgga gggcagctgt ggcttctagc


 


1801
tgcccgggtg gcatccctgt gacccctccc cagtgcctct cctggccttg gaagttgcca


 


1861
ctccagtgcc caccagcctt gtcctaataa aattaagttg catcattttg tctgactagg


 


1921
tgtcctctat aatattatgg ggtggagggg ggtggtttgg agca (SEQ ID NO: 2473)


 







COAGULATION FACTORS


Homo sapiens coagulation factor VII (serum prothrombin conversion


accelerator) (F7), transcript variant 2, mRNA.


ACCESSION NM_019616


VERSION NM_019616.1 GI: 10518502


 


MVSQALRLLCLLLGLQGCLAAVFVTQEEAHGVLHRRRRANAFLEELRPGSLE


RECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCKDQLQS


YICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSL


LADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVN


GAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRV


AQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSL


VSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAG


YSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQ


YIEWLQKLMRSEPRPGVLLRAPFP (SEQ ID NO: 2474)


 








1
agtcccatgg ggaatgtcaa caggcagggg cagcactgca gagatttcat catggtctcc


 


61
caggccctca ggctcctctg ccttctgctt gggcttcagg gctgcctggc tgcagtcttc


 


121
gtaacccagg aggaagccca cggcgtcctg caccggcgcc ggcgcgccaa cgcgttcctg


 


181
gaggagctgc ggccgggctc cctggagagg gagtgcaagg aggagcagtg ctccttcgag


 


241
gaggcccggg agatcttcaa ggacgcggag aggacgaagc tgttctggat ttcttacagt


 


301
gatggggacc agtgtgcctc aagtccatgc cagaatgggg gctcctgcaa ggaccagctc


 


361
cagtcctata tctgcttctg cctccctgcc ttcgagggcc ggaactgtga gacgcacaag


 


421
gatgaccagc tgatctgtgt gaacgagaac ggcggctgtg agcagtactg cagtgaccac


 


481
acgggcacca agcgctcctg tcggtgccac gaggggtact ctctgctggc agacggggtg


 


541
tcctgcacac ccacagttga atatccatgt ggaaaaatac ctattctaga aaaaagaaat


 


601
gccagcaaac cccaaggccg aattgtgggg ggcaaggtgt gccccaaagg ggagtgtcca


 


661
tggcaggtcc tgttgttggt gaatggagct cagttgtgtg gggggaccct gatcaacacc


 


721
atctgggtgg tctccgcggc ccactgtttc gacaaaatca agaactggag gaacctgatc


 


781
gcggtgctgg gcgagcacga cctcagcgag cacgacgggg atgagcagag ccggcgggtg


 


841
gcgcaggtca tcatccccag cacgtacgtc ccgggcacca ccaaccacga catcgcgctg


 


901
ctccgcctgc accagcccgt ggtcctcact gaccatgtgg tgcccctctg cctgcccgaa


 


961
cggacgttct ctgagaggac gctggccttc gtgcgcttct cattggtcag cggctggggc


 


1021
cagctgctgg accgtggcgc cacggccctg gagctcatgg tgctcaacgt gccccggctg


 


1081
atgacccagg actgcctgca gcagtcacgg aaggtgggag actccccaaa tatcacggag


 


1141
tacatgttct gtgccggcta ctcggatggc agcaaggact cctgcaaggg ggacagtgga


 


1201
ggcccacatg ccacccacta ccggggcacg tggtacctga cgggcatcgt cagctggggc


 


1261
cagggctgcg caaccgtggg ccactttggg gtgtacacca gggtctccca gtacatcgag


 


1321
tggctgcaaa agctcatgcg ctcagagcca cgcccaggag tcctcctgcg agccccattt


 


1381
ccctagccca gcagccctgg cctgtggaga gaaagccaag gctgcgtcga actgtcctgg


 


1441
caccaaatcc catatattct tctgcagtta atggggtaga ggagggcatg ggagggaggg


 


1501
agaggtgggg agggagacag agacagaaac agagagagac agagacagag agagactgag


 


1561
ggagagactc tgaggacatg gagagagact caaagagact ccaagattca aagagactaa


 


1621
tagagacaca gagatggaat agaaaagatg agaggcagag gcagacaggc gctggacaga


 


1681
ggggcagggg agtgccaagg ttgtcctgga ggcagacagc ccagctgagc ctccttacct


 


1741
cccttcagcc aagccccacc tgcacgtgat ctgctggccc tcaggctgct gctctgcctt


 


1801
cattgctgga gacagtagag gcatgaacac acatggatgc acacacacac acgccaatgc


 


1861
acacacacag agatatgcac acacacggat gcacacacag atggtcacac agagatacgc


 


1921
aaacacaccg atgcacacgc acatagagat atgcacacac agatgcacac acagatatac


 


1981
acatggatgc acgcacatgc caatgcacgc acacatcagt gcacacggat gcacagagat


 


2041
atgcacacac cgatgtgcgc acacacagat atgcacacac atggatgagc acacacacac


 


2101
caagtgcgca cacacaccga tgtacacaca cagatgcaca cacagatgca cacacaccga


 


2161
tgctgactcc atgtgtgctg tcctctgaag gcggttgttt agctctcact tttctggttc


 


2221
ttatccatta tcatcttcac ttcagacaat tcagaagcat caccatgcat ggtggcgaat


 


2281
gcccccaaac tctcccccaa atgtatttct cccttcgctg ggtgccgggc tgcacagact


 


2341
attccccacc tgcttcccag cttcacaata aacggctgcg tctcctccgc acacctgtgg


 


2401
tgcctgccac cc (SEQ ID NO: 2475)


 







Homo sapiens coagulation factor V (proaccelerin, labile factor)


(F5), mRNA.


ACCESSION NM_000130


VERSION NM_000130.2 GI: 10518500


 


MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTN


SSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKA


DKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTYEWSISEDSG


PTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLL


FAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAHDHISWHLLGMSSGPEL


FSIHFNGQVLEQNHHKVSAITLVSATSTTANMTVGPEGKWIISSLTPKHLQAG


MQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFIAAEEVIWDYAPVIPANM


DKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNPNMKEDGILGPII


RAQVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTMIRAVQ


PGETYTYKWNILEFDEPTENDAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSL


DRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCENPDEVKRDDPKFYES


NIMSTINGYVPESITTLGFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHE


DTLTLFPMRGESVTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDE


DSYEIFEPPESTVMATRKMHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSS


LNQEEEEFNLTALALENGTEFVSSNTDIIVGSNYSSPSNISKFTVNNLAEPQKAP


SHQQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLLSLG


AGEFRSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGSPSG


MRPWEDLPSQDTGSPSRMRPWEDPPSDLLLLKQSNSSKILVGRWHLASEKGS


YEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPKFPRVRHKS


LQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHPLRSEAYNTFSE


RRLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDHNQNSSNDTGQASCP


PGLYQTVPPEEHYQTFPIQDPDQMHSTSDPSHRSSSPELSEMLEYDRSHKSFPT


DISQMSPSSEHEVWQTVISPDLSQVTLSPELSQTNLSPDLSHTTLSPELIQRNLSP


ALGQMPISPDLSHTTLSPDLSHTTLSLDLSQTNLSPELSQTNLSPALGQMPLSPD


LSHTTISLDFSQTNLSPELSHMTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFS


QTNLSPELSQTNLSPALGQMPLSPDPSHTTLSLDLSQTNLSPELSQTNLSPDLSE


MPLFADLSQIPLTPDLDQMTLSPDLGETDLSPNFGQMSLSPDLSQVTLSPDISDT


TLLPDLSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLNDT


FLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPYKTDVRT


NINSSRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRETDIEDSDDIP


EDTTYKKVVFRKYLDSTFTKRDPRGEYEEHLGILGPIIRAEVDDVIQVRFKNLA


SRPYSLHAHGLSYEKSSEGKTYEDDSPEWFKEDNAVQPNSSYTYVWHATERS


GPESPGSACRAWAYYSAVNPEKDIHSGLIGPLLICQKGILHKDSNMPVDMREF


VLLFMTFDEKKSWYYEKKSRSSWRLTSSEMKKSHEFHAINGMIYSLPGLKMY


EQEWVRLHLLNIGGSQDIHVVHFHGQTLLENGNKQHQLGVWPLLPGSFKTLE


MKASKPGWWLLNTEVGENQRAGMQTPFLIMDRDCRMPMGLSTGIISDSQIKA


SEFLGYWEPRLARLNNGGSYNAWSVEKLAAEFASKPWIQVDMQKEVIITGIQ


TQGAKHYLKSCYTTEFYVAYSSNQINWQIFKGNSTRNVMYFNGNSDASTIKE


NQFDPPIVARYIRISPTRAYNRPTLRLELQGCEVNGCSTPLGMENGKIENKQIT


ASSFKKSWWGDYWEPFRARLNAQGRVNAWQAKANNNKQWLEIDLLKIKKI


TAIITQGCKSLSSEMYVKSYTIHYSEQGVEWKPYRLKSSMVDKIFEGNTNTKG


HVKNFFNPPIISRFIRVIPKTWNQSIALRLELFGCDIY′′ (SEQ ID NO: 2476)


 








1
tcattgcagc tgggacagcc cggagtgtgg ttagcagctc ggcaagcgct gcccaggtcc


 


61
tggggtggtg gcagccagcg ggagcaggaa aggaagcatg ttcccaggct gcccacgcct


 


121
ctgggtcctg gtggtcttgg gcaccagctg ggtaggctgg gggagccaag ggacagaagc


 


181
ggcacagcta aggcagttct acgtggctgc tcagggcatc agttggagct accgacctga


 


241
gcccacaaac tcaagtttga atctttctgt aacttccttt aagaaaattg tctacagaga


 


301
gtatgaacca tattttaaga aagaaaaacc acaatctacc atttcaggac ttcttgggcc


 


361
tactttatat gctgaagtcg gagacatcat aaaagttcac tttaaaaata aggcagataa


 


421
gcccttgagc atccatcctc aaggaattag gtacagtaaa ttatcagaag gtgcttctta


 


481
ccttgaccac acattccctg cagagaagat ggacgacgct gtggctccag gccgagaata


 


541
cacctatgaa tggagtatca gtgaggacag tggacccacc catgatgacc ctccatgcct


 


601
cacacacatc tattactccc atgaaaatct gatcgaggat ttcaactctg ggctgattgg


 


661
gcccctgctt atctgtaaaa aagggaccct aactgagggt gggacacaga agacgtttga


 


721
caagcaaatc gtgctactat ttgctgtgtt tgatgaaagc aagagctgga gccagtcatc


 


781
atccctaatg tacacagtca atggatatgt gaatgggaca atgccagata taacagtttg


 


841
tgcccatgac cacatcagct ggcatctgct gggaatgagc tcggggccag aattattctc


 


901
cattcatttc aacggccagg tcctggagca gaaccatcat aaggtctcag ccatcaccct


 


961
tgtcagtgct acatccacta ccgcaaatat gactgtgggc ccagagggaa agtggatcat


 


1021
atcttctctc accccaaaac atttgcaagc tgggatgcag gcttacattg acattaaaaa


 


1081
ctgcccaaag aaaaccagga atcttaagaa aataactcgt gagcagaggc ggcacatgaa


 


1141
gaggtgggaa tacttcattg ctgcagagga agtcatttgg gactatgcac ctgtaatacc


 


1201
agcgaatatg gacaaaaaat acaggtctca gcatttggat aatttctcaa accaaattgg


 


1261
aaaacattat aagaaagtta tgtacacaca gtacgaagat gagtccttca ccaaacatac


 


1321
agtgaatccc aatatgaaag aagatgggat tttgggtcct attatcagag cccaggtcag


 


1381
agacacactc aaaatcgtgt tcaaaaatat ggccagccgc ccctatagca tttaccctca


 


1441
tggagtgacc ttctcgcctt atgaagatga agtcaactct tctttcacct caggcaggaa


 


1501
caacaccatg atcagagcag ttcaaccagg ggaaacctat acttataagt ggaacatctt


 


1561
agagtttgat gaacccacag aaaatgatgc ccagtgctta acaagaccat actacagtga


 


1621
cgtggacatc atgagagaca tcgcctctgg gctaatagga ctacttctaa tctgtaagag


 


1681
cagatccctg gacaggcgag gaatacagag ggcagcagac atcgaacagc aggctgtgtt


 


1741
tgctgtgttt gatgagaaca aaagctggta ccttgaggac aacatcaaca agttttgtga


 


1801
aaatcctgat gaggtgaaac gtgatgaccc caagttttat gaatcaaaca tcatgagcac


 


1861
tatcaatggc tatgtgcctg agagcataac tactcttgga ttctgctttg atgacactgt


 


1921
ccagtggcac ttctgtagtg tggggaccca gaatgaaatt ttgaccatcc acttcactgg


 


1981
gcactcattc atctatggaa agaggcatga ggacaccttg accctcttcc ccatgcgtgg


 


2041
agaatctgtg acggtcacaa tggataatgt tggaacttgg atgttaactt ccatgaattc


 


2101
tagtccaaga agcaaaaagc tgaggctgaa attcagggat gttaaatgta tcccagatga


 


2161
tgatgaagac tcatatgaga tttttgaacc tccagaatct acagtcatgg ctacacggaa


 


2221
aatgcatgat cgtttagaac ctgaagatga agagagtgat gctgactatg attaccagaa


 


2281
cagactggct gcagcattag gaattaggtc attccgaaac tcatcattga accaggaaga


 


2341
agaagagttc aatcttactg ccctagctct ggagaatggc actgaattcg tttcttcgaa


 


2401
cacagatata attgttggtt caaattattc ttccccaagt aatattagta agttcactgt


 


2461
caataacctt gcagaacctc agaaagcccc ttctcaccaa caagccacca cagctggttc


 


2521
cccactgaga cacctcattg gcaagaactc agttctcaat tcttccacag cagagcattc


 


2581
cagcccatat tctgaagacc ctatagagga tcctctacag ccagatgtca cagggatacg


 


2641
tctactttca cttggtgctg gagaattcag aagtcaagaa catgctaagc gtaagggacc


 


2701
caaggtagaa agagatcaag cagcaaagca caggttctcc tggatgaaat tactagcaca


 


2761
taaagttggg agacacctaa gccaagacac tggttctcct tccggaatga ggccctggga


 


2821
ggaccttcct agccaagaca ctggttctcc ttccagaatg aggccctggg aggaccctcc


 


2881
tagtgatctg ttactcttaa aacaaagtaa ctcatctaag attttggttg ggagatggca


 


2941
tttggcttct gagaaaggta gctatgaaat aatccaagat actgatgaag acacagctgt


 


3001
taacaattgg ctgatcagcc cccagaatgc ctcacgtgct tggggagaaa gcacccctct


 


3061
tgccaacaag cctggaaagc agagtggcca cccaaagttt cctagagtta gacataaatc


 


3121
tctacaagta agacaggatg gaggaaagag tagactgaag aaaagccagt ttctcattaa


 


3181
gacacgaaaa aagaaaaaag agaagcacac acaccatgct cctttatctc cgaggacctt


 


3241
tcaccctcta agaagtgaag cctacaacac attttcagaa agaagactta agcattcgtt


 


3301
ggtgcttcat aaatccaatg aaacatctct tcccacagac ctcaatcaga cattgccctc


 


3361
tatggatttt ggctggatag cctcacttcc tgaccataat cagaattcct caaatgacac


 


3421
tggtcaggca agctgtcctc caggtcttta tcagacagtg cccccagagg aacactatca


 


3481
aacattcccc attcaagacc ctgatcaaat gcactctact tcagacccca gtcacagatc


 


3541
ctcttctcca gagctcagtg aaatgcttga gtatgaccga agtcacaagt ccttccccac


 


3601
agatataagt caaatgtccc cttcctcaga acatgaagtc tggcagacag tcatctctcc


 


3661
agacctcagc caggtgaccc tctctccaga actcagccag acaaacctct ctccagacct


 


3721
cagccacacg actctctctc cagaactcat tcagagaaac ctttccccag ccctcggtca


 


3781
gatgcccatt tctccagacc tcagccatac aaccctttct ccagacctca gccatacaac


 


3841
cctttcttta gacctcagcc agacaaacct ctctccagaa ctcagtcaga caaacctttc


 


3901
tccagccctc ggtcagatgc ccctttctcc agacctcagc catacaacca tttctctaga


 


3961
cttcagccag acaaacctct ctccagaact cagccatatg actctctctc cagaactcag


 


4021
tcagacaaac ctttccccag ccctcggtca gatgcccatt tctccagacc tcagccatac


 


4081
aaccctttct ctagacttca gccagacaaa cctctctcca gaactcagtc aaacaaacct


 


4141
ttccccagcc ctcggtcaga tgcccctttc tccagacccc agccatacaa ccctttctct


 


4201
agacctcagc cagacaaacc tctctccaga actcagtcag acaaaccttt ccccagacct


 


4261
cagtgagatg cccctctttg cagatctcag tcaaattccc cttaccccag acctcgacca


 


4321
gatgacactt tctccagacc ttggtgagac agatctttcc ccaaactttg gtcagatgtc


 


4381
cctttcccca gacctcagcc aggtgactct ctctccagac atcagtgaca ccacccttct


 


4441
cccggatctc agccagatat cacctcctcc agaccttgat cagatattct acccttctga


 


4501
atctagtcag tcattgcttc ttcaagaatt taatgagtct tttccttatc cagaccttgg


 


4561
tcagatgcca tctccttcat ctcctactct caatgatact tttctatcaa aggaatttaa


 


4621
tccactggtt atagtgggcc tcagtaaaga tggtacagat tacattgaga tcattccaaa


 


4681
ggaagaggtc cagagcagtg aagatgacta tgctgaaatt gattatgtgc cctatgatga


 


4741
cccctacaaa actgatgtta ggacaaacat caactcctcc agagatcctg acaacattgc


 


4801
agcatggtac ctccgcagca acaatggaaa cagaagaaat tattacattg ctgctgaaga


 


4861
aatatcctgg gattattcag aatttgtaca aagggaaaca gatattgaag actctgatga


 


4921
tattccagaa gataccacat ataagaaagt agtttttcga aagtacctcg acagcacttt


 


4981
taccaaacgt gatcctcgag gggagtatga agagcatctc ggaattcttg gtcctattat


 


5041
cagagctgaa gtggatgatg ttatccaagt tcgttttaaa aatttagcat ccagaccgta


 


5101
ttctctacat gcccatggac tttcctatga aaaatcatca gagggaaaga cttatgaaga


 


5161
tgactctcct gaatggttta aggaagataa tgctgttcag ccaaatagca gttataccta


 


5221
cgtatggcat gccactgagc gatcagggcc agaaagtcct ggctctgcct gtcgggcttg


 


5281
ggcctactac tcagctgtga acccagaaaa agatattcac tcaggcttga taggtcccct


 


5341
cctaatctgc caaaaaggaa tactacataa ggacagcaac atgcctgtgg acatgagaga


 


5401
atttgtctta ctatttatga cctttgatga aaagaagagc tggtactatg aaaagaagtc


 


5461
ccgaagttct tggagactca catcctcaga aatgaaaaaa tcccatgagt ttcacgccat


 


5521
taatgggatg atctacagct tgcctggcct gaaaatgtat gagcaagagt gggtgaggtt


 


5581
acacctgctg aacataggcg gctcccaaga cattcacgtg gttcactttc acggccagac


 


5641
cttgctggaa aatggcaata aacagcacca gttaggggtc tggccccttc tgcctggttc


 


5701
atttaaaact cttgaaatga aggcatcaaa acctggctgg tggctcctaa acacagaggt


 


5761
tggagaaaac cagagagcag ggatgcaaac gccatttctt atcatggaca gagactgtag


 


5821
gatgccaatg ggactaagca ctggtatcat atctgattca cagatcaagg cttcagagtt


 


5881
tctgggttac tgggagccca gattagcaag attaaacaat ggtggatctt ataatgcttg


 


5941
gagtgtagaa aaacttgcag cagaatttgc ctctaaacct tggatccagg tggacatgca


 


6001
aaaggaagtc ataatcacag ggatccagac ccaaggtgcc aaacactacc tgaagtcctg


 


6061
ctataccaca gagttctatg tagcttacag ttccaaccag atcaactggc agatcttcaa


 


6121
agggaacagc acaaggaatg tgatgtattt taatggcaat tcagatgcct ctacaataaa


 


6181
agagaatcag tttgacccac ctattgtggc tagatatatt aggatctctc caactcgagc


 


6241
ctataacaga cctacccttc gattggaact gcaaggttgt gaggtaaatg gatgttccac


 


6301
acccctgggt atggaaaatg gaaagataga aaacaagcaa atcacagctt cttcgtttaa


 


6361
gaaatcttgg tggggagatt actgggaacc cttccgtgcc cgtctgaatg cccagggacg


 


6421
tgtgaatgcc tggcaagcca aggcaaacaa caataagcag tggctagaaa ttgatctact


 


6481
caagatcaag aagataacgg caattataac acagggctgc aagtctctgt cctctgaaat


 


6541
gtatgtaaag agctatacca tccactacag tgagcaggga gtggaatgga aaccatacag


 


6601
gctgaaatcc tccatggtgg acaagatttt tgaaggaaat actaatacca aaggacatgt


 


6661
gaagaacttt ttcaaccccc caatcatttc caggtttatc cgtgtcattc ctaaaacatg


 


6721
gaatcaaagt attgcacttc gcctggaact ctttggctgt gatatttact agaattgaac


 


6781
attcaaaaac ccctggaaga gactctttaa gacctcaaac catttagaat gggcaatgta


 


6841
ttttacgctg tgttaaatgt taacagtttt ccactatttc tctttctttt ctattagtga


 


6901
ataaaatttt atac (SEQ ID NO: 2477)


 







Homo sapiens coagulation factor II (thrombin) (F2), mRNA.


ACCESSION NM_000506


VERSION NM_000506.2 GI: 5922005


 


MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVR


KGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACL


EGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFC


RNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPL


EQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENF


CRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIE


GRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVE


GSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFT


ENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPV


AFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVL


QVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMK


SPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE′′ (SEQ ID NO: 2478)


 








1
aattcctcag tgacccagga gctgacacac tatggcgcac gtccgaggct tgcagctgcc


 


61
tggctgcctg gccctggctg ccctgtgtag ccttgtgcac agccagcatg tgttcctggc


 


121
tcctcagcaa gcacggtcgc tgctccagcg ggtccggcga gccaacacct tcttggagga


 


181
ggtgcgcaag ggcaacctag agcgagagtg cgtggaggag acgtgcagct acgaggaggc


 


241
cttcgaggct ctggagtcct ccacggctac ggatgtgttc tgggccaagt acacagcttg


 


301
tgagacagcg aggacgcctc gagataagct tgctgcatgt ctggaaggta actgtgctga


 


361
gggtctgggt acgaactacc gagggcatgt gaacatcacc cggtcaggca ttgagtgcca


 


421
gctatggagg agtcgctacc cacataagcc tgaaatcaac tccactaccc atcctggggc


 


481
cgacctacag gagaatttct gccgcaaccc cgacagcagc accacgggac cctggtgcta


 


541
cactacagac cccaccgtga ggaggcagga atgcagcatc cctgtctgtg gccaggatca


 


601
agtcactgta gcgatgactc cacgctccga aggctccagt gtgaatctgt cacctccatt


 


661
ggagcagtgt gtccctgatc gggggcagca gtaccagggg cgcctggcgg tgaccacaca


 


721
tgggctcccc tgcctggcct gggccagcgc acaggccaag gccctgagca agcaccagga


 


781
cttcaactca gctgtgcagc tggtggagaa cttctgccgc aacccagacg gggatgagga


 


841
gggcgtgtgg tgctatgtgg ccgggaagcc tggcgacttt gggtactgcg acctcaacta


 


901
ttgtgaggag gccgtggagg aggagacagg agatgggctg gatgaggact cagacagggc


 


961
catcgaaggg cgtaccgcca ccagtgagta ccagactttc ttcaatccga ggacctttgg


 


1021
ctcgggagag gcagactgtg ggctgcgacc tctgttcgag aagaagtcgc tggaggacaa


 


1081
aaccgaaaga gagctcctgg aatcctacat cgacgggcgc attgtggagg gctcggatgc


 


1141
agagatcggc atgtcacctt ggcaggtgat gcttttccgg aagagtcccc aggagctgct


 


1201
gtgtggggcc agcctcatca gtgaccgctg ggtcctcacc gccgcccact gcctcctgta


 


1261
cccgccctgg gacaagaact tcaccgagaa tgaccttctg gtgcgcattg gcaagcactc


 


1321
ccgcacaagg tacgagcgaa acattgaaaa gatatccatg ttggaaaaga tctacatcca


 


1381
ccccaggtac aactggcggg agaacctgga ccgggacatt gccctgatga agctgaagaa


 


1441
gcctgttgcc ttcagtgact acattcaccc tgtgtgtctg cccgacaggg agacggcagc


 


1501
cagcttgctc caggctggat acaaggggcg ggtgacaggc tggggcaacc tgaaggagac


 


1561
gtggacagcc aacgttggta aggggcagcc cagtgtcctg caggtggtga acctgcccat


 


1621
tgtggagcgg ccggtctgca aggactccac ccggatccgc atcactgaca acatgttctg


 


1681
tgctggttac aagcctgatg aagggaaacg aggggatgcc tgtgaaggtg acagtggggg


 


1741
accctttgtc atgaagagcc cctttaacaa ccgctggtat caaatgggca tcgtctcatg


 


1801
gggtgaaggc tgtgaccggg atgggaaata tggcttctac acacatgtgt tccgcctgaa


 


1861
gaagtggata cagaaggtca ttgatcagtt tggagagtag gggccactca tattctgggc


 


1921
tcctggaacc aatcccgtga aagaattatt tttgtgtttc taaaactatg gttcccaata


 


1981
aaagtgactc tcagcgg (SEQ ID NO: 2479)
















TABLE 6







Ala Pro Pro Arg Leu Ile Cys Asp Ser Arg Val Leu Glu Arg Tyr Leu


 1                5                  10                  15


 


Leu Glu Ala Lys Glu Ala Glu Asn Ile Thr Thr Gly Cys Ala Glu His


             20                  25                  30


 


Cys Ser Leu Asn Glu Asn Ile Thr Val Pro Asp Thr Lys Val Asn Phe


         35                  40                  45


 


Tyr Ala Trp Lys Arg Met Glu Val Gly Gln Gln Ala Val Glu Val Trp


     50                  55                  60


 


Gln Gly Leu Ala Leu Leu Ser Glu Ala Val Leu Arg Gly Gln Ala Leu


 65                  70                  75                  80


 


Leu Val Asn Ser Ser Gln Pro Trp Glu Pro Leu Gln Leu His Val Asp


                 85                  90                  95


 


Lys Ala Val Ser Gly Leu Arg Ser Leu Thr Thr Leu Leu Arg Ala Leu


            100                 105                 110


 


Gly Ala Gln Lys Glu Ala Ile Ser Pro Pro Asp Ala Ala Ser Ala Ala


        115                 120                 125


 


Pro Leu Arg Thr Ile Thr Ala Asp Thr Phe Arg Lys Leu Phe Arg Val


    130                 135                 140


 


Tyr Ser Asn Phe Leu Arg Gly Lys Leu Lys Leu Tyr Thr Gly Glu Ala


145                 150                 155                 160


 


Cys Arg Thr Gly Asp (SEQ ID NO: 2480)


 


Ala Pro Pro Arg Leu Ile Cys Asp Ser Arg Val Leu Glu Arg Tyr Leu


  1               5                  10                  15


 


Leu Glu Ala Lys Glu Ala Glu Asn Ile Thr Thr Gly Cys Ala Glu His


             20                  25                  30


 


Cys Ser Leu Asn Glu Asn Ile Thr Val Pro Asp Thr Lys Val Asn Phe


         35                  40                  45


 


Tyr Ala Trp Lys Arg Met Glu Val Gly Gln Gln Ala Val Glu Val Trp


     50                  55                  60


 


Gln Gly Leu Ala Leu Leu Ser Glu Ala Val Leu Arg Gly Gln Ala Leu


 65                  70                  75                  80


 


Leu Val Asn Ser Ser Gln Pro Trp Glu Pro Leu Gln Leu His Val Asp


                 85                  90                  95


 


Lys Ala Val Ser Gly Leu Arg Ser Leu Thr Thr Leu Leu Arg Ala Leu


            100                 105                 110


 


Gly Ala Gln Lys Glu Ala Ile Ser Pro Pro Asp Ala Ala Ser Ala Ala


        115                 120                 125


 


Pro Leu Arg Thr Ile Thr Ala Asp Thr Phe Arg Lys Leu Phe Arg Val


    130                 135                 140


 


Tyr Ser Asn Phe Leu Arg Gly Lys Leu Lys Leu Tyr Thr Gly Glu Ala


145                 150                 155                 160


 


Cys Arg Thr Gly Asp Arg (SEQ ID NO: 2481)


                165
















TABLE 7





(SEQ ID NOS: 2482-4747, respectively,


in order of appearance)















N(Asparagine) as major constituent


Oligonucleotides of peptide motifs containing 3-7


amino acid residues with N(Asparagine) as the


major constituent and T(Threonine) as the minor


constituent


AAY-AAY-ACN, ACN-AAY-AAY, AAY-ACN-AAY, AAY-AAY-AAY-


 


ACN, ACN-AAY-AAY-AAY, AAY-ACN-AAY-AAY, AAY-AAY-ACN-


 


AAY, AAY-AAY-AAY-AAY-ACN, ACN-AAY-AAY-AAY-AAY, AAY-


 


ACN-AAY-AAY-AAY, AAY-AAY-ACN-AAY-AAY, AAY-AAY-AAY-


 


ACN-AAY, AAY-AAY-AAY-ACN-ACN, ACN-ACN-AAY-AAY-AAY,


 


ACN-AAY-ACN-AAY-AAY, ACN-AAY-AAY-ACN-AAY, ACN-AAY-


 


AAY-AAY-ACN, AAY-ACN-ACN-AAY-AAY, AAY-ACN-AAY-ACN-


 


AAY, AAY-ACN-AAY-AAY-ACN, AAY-AAY-ACN-ACN-AAY,


 


AAY-AAY-ACN-AAY-ACN, AAY-AAY-AAY-AAY-AAY-ACN, ACN-


 


AAY-AAY-AAY-AAY-AAY, AAY-ACN-AAY-AAY-AAY-AAY,


 


AAY-AAY-ACN-AAY-AAY-AAY, AAY-AAY-AAY-ACN-AAY-AAY,


 


AAY-AAY-AAY-AAY-ACN-AAY, AAY-AAY-AAY-AAY-ACN-ACN,


 


ACN-ACN-AAY-AAY-AAY-AAY, ACN-AAY-ACN-AAY-AAY-AAY,


 


ACN-AAY-AAY-ACN-AAY-AAY, ACN-AAY-AAY-AAY-ACN-AAY,


 


ACN-AAY-AAY-AAY-AAY-ACN, AAY-ACN-ACN-AAY-AAY-AAY,


 


AAY-ACN-AAY-ACN-AAY-AAY, AAY-ACN-AAY-AAY-ACN-AAY,


 


AAY-ACN-AAY-AAY-AAY-ACN, AAY-AAY-ACN-ACN-AAY-AAY,


 


AAY-AAY-ACN-AAY-ACN-AAY, AAY-AAY-ACN-AAY-AAY-ACN,


 


AAY-AAY-AAY-ACN-ACN-AAY, AAY-AAY-AAY-ACN-AAY-ACN,


 


AAY-AAY-AAY-AAY-ACN-ACN-ACN, ACN-ACN-ACN-AAY-AAY-


 


AAY-AAY, ACN-AAY-ACN-ACN-AAY-AAY-AAY, ACN-AAY-ACN-


 


AAY-ACN-AAY-AAY, ACN-AAY-ACN-AAY-AAY-ACN-AAY, ACN-


 


AAY-ACN-AAY-AAY-AAY-ACN, ACN-AAY-AAY-ACN-ACN-AAY-


 


AAY, ACN-AAY-AAY-ACN-AAY-ACN-AAY, ACN-AAY-AAY-ACN-


 


AAY-AAY-ACN, ACN-AAY-AAY-AAY-ACN-AAY-ACN, ACN-AAY-


 


AAY-AAY-ACN-ACN-AAY, ACN-AAY-AAY-AAY-AAY-ACN-ACN,


 


ACN-ACN-AAY-ACN-AAY-AAY-AAY, ACN-ACN-AAY-AAY-ACN-


 


AAY-AAY, ACN-ACN-AAY-AAY-AAY-ACN-AAY, ACN-ACN-AAY-


 


AAY-AAY-AAY-ACN, AAY-ACN-ACN-ACN-AAY-AAY-AAY, AAY-


 


ACN-ACN-AAY-ACN-AAY-AAY, AAY-ACN-ACN-AAY-AAY-ACN-


 


AAY, AAY-ACN-ACN-AAY-AAY-AAY-ACN, AAY-ACN-AAY-ACN-


 


ACN-AAY-AAY, AAY-ACN-AAY-AAY-ACN-ACN-AAY, AAY-ACN-


 


AAY-AAY-AAY-ACN-ACN, AAY-ACN-AAY-ACN-AAY-ACN-AAY,


 


AAY-ACN-AAY-ACN-AAY-AAY-ACN, AAY-ACN-AAY-AAY-ACN-


 


AAY-ACN, AAY-AAY-ACN-ACN-ACN-AAY-AAY, AAY-AAY-ACN-


 


ACN-AAY-ACN-AAY, AAY-AAY-ACN-ACN-AAY-AAY-ACN, AAY-


 


AAY-ACN-AAY-ACN-ACN-AAY, AAY-AAY-ACN-AAY-ACN-AAY-


 


ACN, AAY-AAY-ACN-AAY-AAY-ACN-ACN, AAY-AAY-AAY-ACN-


 


ACN-ACN-AAY, AAY-AAY-AAY-ACN-ACN-AAY-ACN, AAY-AAY-


 


AAY-ACN-AAY-ACN-ACN, AAY-AAY-AAY-AAY-AAY-ACN-ACN,


 


ACN-ACN-AAY-AAY-AAY-AAY-AAY, ACN-AAY-ACN-AAY-AAY-


 


AAY-AAY, ACN-AAY-AAY-ACN-AAY-AAY-AAY, ACN-AAY-AAY-


 


AAY-ACN-AAY-AAY, ACN-AAY-AAY-AAY-AAY-ACN-AAY, ACN-


 


AAY-AAY-AAY-AAY-AAY-ACN, AAY-ACN-ACN-AAY-AAY-AAY-


 


AAY, AAY-ACN-AAY-ACN-AAY-AAY-AAY, AAY-ACN-AAY-AAY-


 


ACN-AAY-AAY, AAY-ACN-AAY-AAY-AAY-ACN-AAY, AAY-ACN-


 


AAY-AAY-AAY-AAY-ACN, AAY-AAY-ACN-ACN-AAY-AAY-AAY,


 


AAY-AAY-ACN-AAY-ACN-AAY-AAY, AAY-AAY-ACN-AAY-AAY-


 


ACN-AAY, AAY-AAY-ACN-AAY-AAY-AAY-ACN, AAY-AAY-AAY-


 


ACN-ACN-AAY-AAY, AAY-AAY-AAY-ACN-AAY-ACN-AAY, AAY-


 


AAY-AAY-ACN-AAY-AAY-ACN, AAY-AAY-AAY-AAY-ACN-ACN-


 


AAY, AAY-AAY-AAY-AAY-ACN-AAY-ACN-AAY-AAY-AAY-AAY-


 


AAY-AAY-ACN, ACN-AAY-AAY-AAY-AAY-AAY-AAY, AAY-ACN-


 


AAY-AAY-AAY-AAY-AAY, AAY-AAY-ACN-AAY-AAY-AAY-AAY,


 


AAY-AAY-AAY-ACN-AAY-AAY-AAY, AAY-AAY-AAY-AAY-ACN-


 


AAY-AAY, AAY-AAY-AAY-AAY-AAY-ACN-AAY


 


Oligonucleotides of peptide motifs containing 3-7


amino acid residues with N(Asparagine) as the major


constituent and A(Alanine) as the minor constituent


AAY-AAY-GCN, GCN-AAY-AAY, AAY-GCN-AAY, AAY-AAY-AAY-


 


GCN, GCN-AAY-AAY-AAY, AAY-GCN-AAY-AAY, AAY-AAY-GCN-


 


AAY, AAY-AAY-AAY-AAY-GCN, GCN-AAY-AAY-AAY-AAY, AAY-


 


GCN-AAY-AAY-AAY, AAY-AAY-GCN-AAY-AAY, AAY-AAY-AAY-


 


GCN-AAY, AAY-AAY-AAY-GCN-GCN, GCN-GCN-AAY-AAY-AAY,


 


GCN-AAY-GCN-AAY-AAY, GCN-AAY-AAY-GCN-AAY, GCN-AAY-


 


AAY-AAY-GCN, AAY-GCN-GCN-AAY-AAY, AAY-GCN-AAY-GCN-


 


AAY, AAY-GCN-AAY-AAY-GCN, AAY-AAY-GCN-GCN-AAY, AAY-


 


AAY-GCN-AAY-GCN, AAY-AAY-AAY-AAY-AAY-GCN, GCN-AAY-


 


AAY-AAY-AAY-AAY, AAY-GCN-AAY-AAY-AAY-AAY, AAY-AAY-


 


GCN-AAY-AAY-AAY, AAY-AAY-AAY-GCN-AAY-AAY, AAY-AAY-


 


AAY-AAY-GCN-AAY, AAY-AAY-AAY-AAY-GCN-GCN, GCN-GCN-


 


AAY-AAY-AAY-AAY, GCN-AAY-GCN-AAY-AAY-AAY, GCN-AAY-


 


AAY-GCN-AAY-AAY, GCN-AAY-AAY-AAY-GCN-AAY, GCN-AAY-


 


AAY-AAY-AAY-GCN, AAY-GCN-GCN-AAY-AAY-AAY, AAY-GCN-


 


AAY-GCN-AAY-AAY, AAY-GCN-AAY-AAY-GCN-AAY, AAY-GCN-


 


AAY-AAY-AAY-GCN, AAY-AAY-GCN-GCN-AAY-AAY, AAY-AAY-


 


GCN-AAY-GCN-AAY, AAY-AAY-GCN-AAY-AAY-GCN, AAY-AAY-


 


AAY-GCN-GCN-AAY, AAY-AAY-AAY-GCN-AAY-GCN, AAY-AAY-


 


AAY-AAY-GCN-GCN-GCN, GCN-GCN-GCN-AAY-AAY-AAY-AAY,


 


GCN-AAY-GCN-GCN-AAY-AAY-AAY, GCN-AAY-GCN-AAY-GCN-


 


AAY-AAY, GCN-AAY-GCN-AAY-AAY-GCN-AAY, GCN-AAY-GCN-


 


AAY-AAY-AAY-GCN, GCN-AAY-AAY-GCN-GCN-AAY-AAY, GCN-


 


AAY-AAY-GCN-AAY-GCN-AAY, GCN-AAY-AAY-GCN-AAY-AAY-


 


GCN, GCN-AAY-AAY-AAY-GCN-AAY-GCN, GCN-AAY-AAY-AAY-


 


GCN-GCN-AAY, GCN-AAY-AAY-AAY-AAY-GCN-GCN, GCN-GCN-


 


AAY-GCN-AAY-AAY-AAY, GCN-GCN-AAY-AAY-GCN-AAY-AAY,


 


GCN-GCN-AAY-AAY-AAY-GCN-AAY, GCN-GCN-AAY-AAY-AAY-


 


AAY-GCN, AAY-GCN-GCN-GCN-AAY-AAY-AAY, AAY-GCN-GCN-


 


AAY-GCN-AAY-AAY, AAY-GCN-GCN-AAY-AAY-GCN-AAY, AAY-


 


GCN-GCN-AAY-AAY-AAY-GCN, AAY-GCN-AAY-GCN-GCN-AAY-


 


AAY, AAY-GCN-AAY-AAY-GCN-GCN-AAY, AAY-GCN-AAY-AAY-


 


AAY-GCN-GCN, AAY-GCN-AAY-GCN-AAY-GCN-AAY, AAY-GCN-


 


AAY-GCN-AAY-AAY-GCN, AAY-GCN-AAY-AAY-GCN-AAY-GCN,


 


AAY-AAY-GCN-GCN-GCN-AAY-AAY, AAY-AAY-GCN-GCN-AAY-


 


GCN-AAY, AAY-AAY-GCN-GCN-AAY-AAY-GCN, AAY-AAY-GCN-


 


AAY-GCN-GCN-AAY, AAY-AAY-GCN-AAY-GCN-AAY-GCN, AAY-


 


AAY-GCN-AAY-AAY-GCN-GCN, AAY-AAY-AAY-GCN-GCN-GCN-


 


AAY, AAY-AAY-AAY-GCN-GCN-AAY-GCN, AAY-AAY-AAY-GCN-


 


AAY-GCN-GCN, AAY-AAY-AAY-AAY-AAY-GCN-GCN, GCN-GCN-


 


AAY-AAY-AAY-AAY-AAY, GCN-AAY-GCN-AAY-AAY-AAY-AAY,


 


GCN-AAY-AAY-GCN-AAY-AAY-AAY, GCN-AAY-AAY-AAY-GCN-


 


AAY-AAY, GCN-AAY-AAY-AAY-AAY-GCN-AAY, GCN-AAY-AAY-


 


AAY-AAY-AAY-GCN, AAY-GCN-GCN-AAY-AAY-AAY-AAY, AAY-


 


GCN-AAY-GCN-AAY-AAY-AAY, AAY-GCN-AAY-AAY-GCN-AAY-


 


AAY, AAY-GCN-AAY-AAY-AAY-GCN-AAY, AAY-GCN-AAY-AAY-


 


AAY-AAY-GCN, AAY-AAY-GCN-GCN-AAY-AAY-AAY, AAY-AAY-


 


GCN-AAY-GCN-AAY-AAY, AAY-AAY-GCN-AAY-AAY-GCN-AAY,


 


AAY-AAY-GCN-AAY-AAY-AAY-GCN, AAY-AAY-AAY-GCN-GCN-


 


AAY-AAY, AAY-AAY-AAY-GCN-AAY-GCN-AAY, AAY-AAY-AAY-


 


GCN-AAY-AAY-GCN, AAY-AAY-AAY-AAY-GCN-GCN-AAY, AAY-


 


AAY-AAY-AAY-GCN-AAY-GCN-AAY-AAY-AAY-AAY-AAY-AAY-


 


GCN, GCN-AAY-AAY-AAY-AAY-AAY-AAY, AAY-GCN-AAY-AAY-


 


AAY-AAY-AAY, AAY-AAY-GCN-AAY-AAY-AAY-AAY, AAY-AAY-


 


AAY-GCN-AAY-AAY-AAY, AAY-AAY-AAY-AAY-GCN-AAY-AAY, 


 


AAY-AAY-AAY-AAY-AAY-GCN-AAY


 


Oligonucleotides of peptide motifs containing 3-7


amino acid residues with N(Asparagine) as the major


constituent and S(Serine) as the minor constituent


AAY-AAY-AGY, AGY-AAY-AAY, AAY-AGY-AAY, AAY-AAY-AAY-


 


AGY, AGY-AAY-AAY-AAY, AAY-AGY-AAY-AAY, AAY-AAY-AGY-


 


AAY, AAY-AAY-AAY-AAY-AGY, AGY-AAY-AAY-AAY-AAY, AAY-


 


AGY-AAY-AAY-AAY, AAY-AAY-AGY-AAY-AAY, AAY-AAY-AAY-


 


AGY-AAY, AAY-AAY-AAY-AGY-AGY, AGY-AGY-AAY-AAY-AAY,


 


AGY-AAY-AGY-AAY-AAY, AGY-AAY-AAY-AGY-AAY, AGY-AAY-


 


AAY-AAY-AGY, AAY-AGY-AGY-AAY-AAY, AAY-AGY-AAY-AGY-


 


AAY, AAY-AGY-AAY-AAY-AGY, AAY-AAY-AGY-AGY-AAY, AAY-


 


AAY-AGY-AAY-AGY, AAY-AAY-AAY-AAY-AAY-AGY, AGY-AAY-


 


AAY-AAY-AAY-AAY, AAY-AGY-AAY-AAY-AAY-AAY, AAY-AAY-


 


AGY-AAY-AAY-AAY, AAY-AAY-AAY-AGY-AAY-AAY, AAY-AAY-


 


AAY-AAY-AGY-AAY, AAY-AAY-AAY-AAY-AGY-AGY, AGY-AGY-


 


AAY-AAY-AAY-AAY, AGY-AAY-AGY-AAY-AAY-AAY, AGY-AAY-


 


AAY-AGY-AAY-AAY, AGY-AAY-AAY-AAY-AGY-AAY, AGY-AAY-


 


AAY-AAY-AAY-AGY, AAY-AGY-AGY-AAY-AAY-AAY, AAY-AGY-


 


AAY-AGY-AAY-AAY, AAY-AGY-AAY-AAY-AGY-AAY, AAY-AGY-


 


AAY-AAY-AAY-AGY, AAY-AAY-AGY-AGY-AAY-AAY, AAY-AAY-


 


AGY-AAY-AGY-AAY, AAY-AAY-AGY-AAY-AAY-AGY, AAY-AAY-


 


AAY-AGY-AGY-AAY, AAY-AAY-AAY-AGY-AAY-AGY, AAY-AAY-


 


AAY-AAY-AGY-AGY-AGY, AGY-AGY-AGY-AAY-AAY-AAY-AAY,


 


AGY-AAY-AGY-AGY-AAY-AAY-AAY, AGY-AAY-AGY-AAY-AGY-


 


AAY-AAY, AGY-AAY-AGY-AAY-AAY-AGY-AAY, AGY-AAY-AGY-


 


AAY-AAY-AAY-AGY, AGY-AAY-AAY-AGY-AGY-AAY-AAY, AGY-


 


AAY-AAY-AGY-AAY-AGY-AAY, AGY-AAY-AAY-AGY-AAY-AAY-


 


AGY, AGY-AAY-AAY-AAY-AGY-AAY-AGY, AGY-AAY-AAY-AAY-


 


AGY-AGY-AAY, AGY-AAY-AAY-AAY-AAY-AGY-AGY, AGY-AGY-


 


AAY-AGY-AAY-AAY-AAY, AGY-AGY-AAY-AAY-AGY-AAY-AAY,


 


AGY-AGY-AAY-AAY-AAY-AGY-AAY, AGY-AGY-AAY-AAY-AAY-


 


AAY-AGY, AAY-AGY-AGY-AGY-AAY-AAY-AAY, AAY-AGY-AGY-


 


AAY-AGY-AAY-AAY, AAY-AGY-AGY-AAY-AAY-AGY-AAY, AAY-


 


AGY-AGY-AAY-AAY-AAY-AGY, AAY-AGY-AAY-AGY-AGY-AAY-


 


AAY, AAY-AGY-AAY-AAY-AGY-AGY-AAY, AAY-AGY-AAY-AAY-


 


AAY-AGY-AGY, AAY-AGY-AAY-AGY-AAY-AGY-AAY, AAY-AGY-


 


AAY-AGY-AAY-AAY-AGY, AAY-AGY-AAY-AAY-AGY-AAY-AGY, 


 


AAY-AAY-AGY-AGY-AGY-AAY-AAY, AAY-AAY-AGY-AGY-AAY-


 


AGY-AAY, AAY-AAY-AGY-AGY-AAY-AAY-AGY, AAY-AAY-AGY-


 


AAY-AGY-AGY-AAY, AAY-AAY-AGY-AAY-AGY-AAY-AGY, AAY-


 


AAY-AGY-AAY-AAY-AGY-AGY, AAY-AAY-AAY-AGY-AGY-AGY-


 


AAY, AAY-AAY-AAY-AGY-AGY-AAY-AGY, AAY-AAY-AAY-AGY-


 


AAY-AGY-AGY, AAY-AAY-AAY-AAY-AAY-AGY-AGY, AGY-AGY-


 


AAY-AAY-AAY-AAY-AAY, AGY-AAY-AGY-AAY-AAY-AAY-AAY,


 


AGY-AAY-AAY-AGY-AAY-AAY-AAY, AGY-AAY-AAY-AAY-AGY-


 


AAY-AAY, AGY-AAY-AAY-AAY-AAY-AGY-AAY, AGY-AAY-AAY-


 


AAY-AAY-AAY-AGY, AAY-AGY-AGY-AAY-AAY-AAY-AAY, AAY-


 


AGY-AAY-AGY-AAY-AAY-AAY, AAY-AGY-AAY-AAY-AGY-AAY-


 


AAY, AAY-AGY-AAY-AAY-AAY-AGY-AAY, AAY-AGY-AAY-AAY-


 


AAY-AAY-AGY, AAY-AAY-AGY-AGY-AAY-AAY-AAY, AAY-AAY-


 


AGY-AAY-AGY-AAY-AAY, AAY-AAY-AGY-AAY-AAY-AGY-AAY, 


 


AAY-AAY-AGY-AAY-AAY-AAY-AGY, AAY-AAY-AAY-AGY-AGY-


 


AAY-AAY, AAY-AAY-AAY-AGY-AAY-AGY-AAY, AAY-AAY-AAY-


 


AGY-AAY-AAY-AGY, AAY-AAY-AAY-AAY-AGY-AGY-AAY, AAY-


 


AAY-AAY-AAY-AGY-AAY-AGY-AAY-AAY-AAY-AAY-AAY-AAY-AGY, 


 


AGY-AAY-AAY-AAY-AAY-AAY-AAY, AAY-AGY-AAY-AAY-AAY-


 


AAY-AAY, AAY-AAY-AGY-AAY-AAY-AAY-AAY, AAY-AAY-AAY-


 


AGY-AAY-AAY-AAY, AAY-AAY-AAY-AAY-AGY-AAY-AAY, AAY-


 


AAY-AAY-AAY-AAY-AGY-AAY


 


Oligonucleotides of peptide motifs containing 3-7 


amino acid residues with N(Asparagine) as the major


constituent and


Q(Glutamine) as the minor constituent


AAY-AAY-CAR, CAR-AAY-AAY, AAY-CAR-AAY, AAY-AAY-AAY-


 


CAR, CAR-AAY-AAY-AAY, AAY-CAR-AAY-AAY, AAY-AAY-CAR-


 


AAY, AAY-AAY-AAY-AAY-CAR, CAR-AAY-AAY-AAY-AAY, AAY-


 


CAR-AAY-AAY-AAY, AAY-AAY-CAR-AAY-AAY, AAY-AAY-AAY-


 


CAR-AAY, AAY-AAY-AAY-CAR-CAR, CAR-CAR-AAY-AAY-AAY, 


 


CAR-AAY-CAR-AAY-AAY, CAR-AAY-AAY-CAR-AAY, CAR-AAY-


 


AAY-AAY-CAR, AAY-CAR-CAR-AAY-AAY, AAY-CAR-AAY-CAR-


 


AAY, AAY-CAR-AAY-AAY-CAR, AAY-AAY-CAR-CAR-AAY, AAY-


 


AAY-CAR-AAY-CAR, AAY-AAY-AAY-AAY-AAY-CAR, CAR-AAY-


 


AAY-AAY-AAY-AAY, AAY-CAR-AAY-AAY-AAY-AAY, AAY-AAY-


 


CAR-AAY-AAY-AAY, AAY-AAY-AAY-CAR-AAY-AAY, AAY-AAY-


 


AAY-AAY-CAR-AAY, AAY-AAY-AAY-AAY-CAR-CAR, CAR-CAR-


 


AAY-AAY-AAY-AAY, CAR-AAY-CAR-AAY-AAY-AAY, CAR-AAY-


 


AAY-CAR-AAY-AAY, CAR-AAY-AAY-AAY-CAR-AAY, CAR-AAY-


 


AAY-AAY-AAY-CAR, AAY-CAR-CAR-AAY-AAY-AAY, AAY-CAR-


 


AAY-CAR-AAY-AAY, AAY-CAR-AAY-AAY-CAR-AAY, AAY-CAR-


 


AAY-AAY-AAY-CAR, AAY-AAY-CAR-CAR-AAY-AAY, AAY-AAY-


 


CAR-AAY-CAR-AAY, AAY-AAY-CAR-AAY-AAY-CAR, AAY-AAY-


 


AAY-CAR-CAR-AAY, AAY-AAY-AAY-CAR-AAY-CAR, AAY-AAY-


 


AAY-AAY-CAR-CAR-CAR, CAR-CAR-CAR-AAY-AAY-AAY-AAY, 


 


CAR-AAY-CAR-CAR-AAY-AAY-AAY, CAR-AAY-CAR-AAY-CAR-


 


AAY-AAY, CAR-AAY-CAR-AAY-AAY-CAR-AAY, CAR-AAY-CAR-


 


AAY-AAY-AAY-CAR, CAR-AAY-AAY-CAR-CAR-AAY-AAY, CAR-


 


AAY-AAY-CAR-AAY-CAR-AAY, CAR-AAY-AAY-CAR-AAY-AAY-


 


CAR, CAR-AAY-AAY-AAY-CAR-AAY-CAR, CAR-AAY-AAY-AAY-


 


CAR-CAR-AAY, CAR-AAY-AAY-AAY-AAY-CAR-CAR, CAR-CAR-


 


AAY-CAR-AAY-AAY-AAY, CAR-CAR-AAY-AAY-CAR-AAY-AAY, 


 


CAR-CAR-AAY-AAY-AAY-CAR-AAY, CAR-CAR-AAY-AAY-AAY-


 


AAY-CAR, AAY-CAR-CAR-CAR-AAY-AAY-AAY, AAY-CAR-CAR-


 


AAY-CAR-AAY-AAY, AAY-CAR-CAR-AAY-AAY-CAR-AAY, AAY-


 


CAR-CAR-AAY-AAY-AAY-CAR, AAY-CAR-AAY-CAR-CAR-AAY-


 


AAY, AAY-CAR-AAY-AAY-CAR-CAR-AAY, AAY-CAR-AAY-AAY-


 


AAY-CAR-CAR, AAY-CAR-AAY-CAR-AAY-CAR-AAY, AAY-CAR-


 


AAY-CAR-AAY-AAY-CAR, AAY-CAR-AAY-AAY-CAR-AAY-CAR, 


 


AAY-AAY-CAR-CAR-CAR-AAY-AAY, AAY-AAY-CAR-CAR-AAY-


 


CAR-AAY, AAY-AAY-CAR-CAR-AAY-AAY-CAR, AAY-AAY-CAR-


 


AAY-CAR-CAR-AAY, AAY-AAY-CAR-AAY-CAR-AAY-CAR, AAY-


 


AAY-CAR-AAY-AAY-CAR-CAR, AAY-AAY-AAY-CAR-CAR-CAR-


 


AAY, AAY-AAY-AAY-CAR-CAR-AAY-CAR, AAY-AAY-AAY-CAR-


 


AAY-CAR-CAR, AAY-AAY-AAY-AAY-AAY-CAR-CAR, CAR-CAR-


 


AAY-AAY-AAY-AAY-AAY, CAR-AAY-CAR-AAY-AAY-AAY-AAY, 


 


CAR-AAY-AAY-CAR-AAY-AAY-AAY, CAR-AAY-AAY-AAY-CAR-


 


AAY-AAY, CAR-AAY-AAY-AAY-AAY-CAR-AAY, CAR-AAY-AAY-


 


AAY-AAY-AAY-CAR, AAY-CAR-CAR-AAY-AAY-AAY-AAY, AAY-


 


CAR-AAY-CAR-AAY-AAY-AAY, AAY-CAR-AAY-AAY-CAR-AAY-


 


AAY, AAY-CAR-AAY-AAY-AAY-CAR-AAY, AAY-CAR-AAY-AAY-


 


AAY-AAY-CAR, AAY-AAY-CAR-CAR-AAY-AAY-AAY, AAY-AAY-


 


CAR-AAY-CAR-AAY-AAY, AAY-AAY-CAR-AAY-AAY-CAR-AAY, 


 


AAY-AAY-CAR-AAY-AAY-AAY-CAR, AAY-AAY-AAY-CAR-CAR-


 


AAY-AAY, AAY-AAY-AAY-CAR-AAY-CAR-AAY, AAY-AAY-AAY-


 


CAR-AAY-AAY-CAR, AAY-AAY-AAY-AAY-CAR-CAR-AAY, AAY-


 


AAY-AAY-AAY-CAR-AAY-CAR-AAY-AAY-AAY-AAY-AAY-AAY-CAR, 


 


CAR-AAY-AAY-AAY-AAY-AAY-AAY, AAY-CAR-AAY-AAY-AAY-


 


AAY-AAY, AAY-AAY-CAR-AAY-AAY-AAY-AAY, AAY-AAY-AAY-


 


CAR-AAY-AAY-AAY, AAY-AAY-AAY-AAY-CAR-AAY-AAY, AAY-


 


AAY-AAY-AAY-AAY-CAR-AAY


 


Oligonucleotides of peptide motifs containing 3-7


amino acid residues with N(Asparagine) as the major


constituent and


E(Glutamic Acid) as the minor constituent


AAY-AAY-GAR, GAR-AAY-AAY, AAY-GAR-AAY, AAY-AAY-AAY-


 


GAR, GAR-AAY-AAY-AAY, AAY-GAR-AAY-AAY, AAY-AAY-GAR-


 


AAY, AAY-AAY-AAY-AAY-GAR, GAR-AAY-AAY-AAY-AAY, AAY-


 


GAR-AAY-AAY-AAY, AAY-AAY-GAR-AAY-AAY, AAY-AAY-AAY-


 


GAR-AAY, AAY-AAY-AAY-GAR-GAR, GAR-GAR-AAY-AAY-AAY, 


 


GAR-AAY-GAR-AAY-AAY, GAR-AAY-AAY-GAR-AAY, GAR-AAY-


 


AAY-AAY-GAR, AAY-GAR-GAR-AAY-AAY, AAY-GAR-AAY-GAR-


 


AAY, AAY-GAR-AAY-AAY-GAR, AAY-AAY-GAR-GAR-AAY, AAY-


 


AAY-GAR-AAY-GAR, AAY-AAY-AAY-AAY-AAY-GAR, GAR-AAY-


 


AAY-AAY-AAY-AAY, AAY-GAR-AAY-AAY-AAY-AAY, AAY-AAY-


 


GAR-AAY-AAY-AAY, AAY-AAY-AAY-GAR-AAY-AAY, AAY-AAY-


 


AAY-AAY-GAR-AAY, AAY-AAY-AAY-AAY-GAR-GAR, GAR-GAR-


 


AAY-AAY-AAY-AAY, GAR-AAY-GAR-AAY-AAY-AAY, GAR-AAY-


 


AAY-GAR-AAY-AAY, GAR-AAY-AAY-AAY-GAR-AAY, GAR-AAY-


 


AAY-AAY-AAY-GAR, AAY-GAR-GAR-AAY-AAY-AAY, AAY-GAR-


 


AAY-GAR-AAY-AAY, AAY-GAR-AAY-AAY-GAR-AAY, AAY-GAR-


 


AAY-AAY-AAY-GAR, AAY-AAY-GAR-GAR-AAY-AAY, AAY-AAY-


 


GAR-AAY-GAR-AAY, AAY-AAY-GAR-AAY-AAY-GAR, AAY-AAY-


 


AAY-GAR-GAR-AAY, AAY-AAY-AAY-GAR-AAY-GAR, AAY-AAY-


 


AAY-AAY-GAR-GAR-GAR, GAR-GAR-GAR-AAY-AAY-AAY-AAY, 


 


GAR-AAY-GAR-GAR-AAY-AAY-AAY, GAR-AAY-GAR-AAY-GAR-


 


AAY-AAY, GAR-AAY-GAR-AAY-AAY-GAR-AAY, GAR-AAY-GAR-


 


AAY-AAY-AAY-GAR, GAR-AAY-AAY-GAR-GAR-AAY-AAY, GAR-


 


AAY-AAY-GAR-AAY-GAR-AAY, GAR-AAY-AAY-GAR-AAY-AAY-


 


GAR, GAR-AAY-AAY-AAY-GAR-AAY-GAR, GAR-AAY-AAY-AAY-


 


GAR-GAR-AAY, GAR-AAY-AAY-AAY-AAY-GAR-GAR, GAR-GAR-


 


AAY-GAR-AAY-AAY-AAY, GAR-GAR-AAY-AAY-GAR-AAY-AAY, 


 


GAR-GAR-AAY-AAY-AAY-GAR-AAY, GAR-GAR-AAY-AAY-AAY-


 


AAY-GAR, AAY-GAR-GAR-GAR-AAY-AAY-AAY, AAY-GAR-GAR-


 


AAY-GAR-AAY-AAY, AAY-GAR-GAR-AAY-AAY-GAR-AAY, AAY-


 


GAR-GAR-AAY-AAY-AAY-GAR, AAY-GAR-AAY-GAR-GAR-AAY-


 


AAY, AAY-GAR-AAY-AAY-GAR-GAR-AAY, AAY-GAR-AAY-AAY-


 


AAY-GAR-GAR, AAY-GAR-AAY-GAR-AAY-GAR-AAY, AAY-GAR-


 


AAY-GAR-AAY-AAY-GAR, AAY-GAR-AAY-AAY-GAR-AAY-GAR, 


 


AAY-AAY-GAR-GAR-GAR-AAY-AAY, AAY-AAY-GAR-GAR-AAY-


 


GAR-AAY, AAY-AAY-GAR-GAR-AAY-AAY-GAR, AAY-AAY-GAR-


 


AAY-GAR-GAR-AAY, AAY-AAY-GAR-AAY-GAR-AAY-GAR, AAY-


 


AAY-GAR-AAY-AAY-GAR-GAR, AAY-AAY-AAY-GAR-GAR-GAR-


 


AAY, AAY-AAY-AAY-GAR-GAR-AAY-GAR, AAY-AAY-AAY-GAR-


 


AAY-GAR-GAR, AAY-AAY-AAY-AAY-AAY-GAR-GAR, GAR-GAR-


 


AAY-AAY-AAY-AAY-AAY, GAR-AAY-GAR-AAY-AAY-AAY-AAY, 


 


GAR-AAY-AAY-GAR-AAY-AAY-AAY, GAR-AAY-AAY-AAY-GAR-


 


AAY-AAY, GAR-AAY-AAY-AAY-AAY-GAR-AAY, GAR-AAY-AAY-


 


AAY-AAY-AAY-GAR, AAY-GAR-GAR-AAY-AAY-AAY-AAY, AAY-


 


GAR-AAY-GAR-AAY-AAY-AAY, AAY-GAR-AAY-AAY-GAR-AAY-


 


AAY, AAY-GAR-AAY-AAY-AAY-GAR-AAY, AAY-GAR-AAY-AAY-


 


AAY-AAY-GAR, AAY-AAY-GAR-GAR-AAY-AAY-AAY, AAY-AAY-


 


GAR-AAY-GAR-AAY-AAY, AAY-AAY-GAR-AAY-AAY-GAR-AAY, 


 


AAY-AAY-GAR-AAY-AAY-AAY-GAR, AAY-AAY-AAY-GAR-GAR-


 


AAY-AAY, AAY-AAY-AAY-GAR-AAY-GAR-AAY, AAY-AAY-AAY-


 


GAR-AAY-AAY-GAR, AAY-AAY-AAY-AAY-GAR-GAR-AAY, AAY-


 


AAY-AAY-AAY-GAR-AAY-GAR-AAY-AAY-AAY-AAY-AAY-AAY-


 


GAR, GAR-AAY-AAY-AAY-AAY-AAY-AAY, AAY-GAR-AAY-AAY-


 


AAY-AAY-AAY, AAY-AAY-GAR-AAY-AAY-AAY-AAY, AAY-AAY-


 


AAY-GAR-AAY-AAY-AAY, AAY-AAY-AAY-AAY-GAR-AAY-AAY, 


 


AAY-AAY-AAY-AAY-AAY-GAR-AAY


 


Oligonucleotides of peptide motifs containing 3-7


amino acid residues with N(Asparagine) as the major


constituent and


H(Histidine) as the minor constituent


AAY-AAY-CAY, CAY-AAY-AAY, AAY-CAY-AAY, AAY-AAY-AAY-


 


CAY, CAY-AAY-AAY-AAY, AAY-CAY-AAY-AAY, AAY-AAY-CAY-


 


AAY, AAY-AAY-AAY-AAY-CAY, CAY-AAY-AAY-AAY-AAY, AAY-


 


CAY-AAY-AAY-AAY, AAY-AAY-CAY-AAY-AAY, AAY-AAY-AAY-


 


CAY-AAY, AAY-AAY-AAY-CAY-CAY, CAY-CAY-AAY-AAY-AAY, 


 


CAY-AAY-CAY-AAY-AAY, CAY-AAY-AAY-CAY-AAY, CAY-AAY-


 


AAY-AAY-CAY, AAY-CAY-CAY-AAY-AAY, AAY-CAY-AAY-CAY-


 


AAY, AAY-CAY-AAY-AAY-CAY, AAY-AAY-CAY-CAY-AAY, AAY-


 


AAY-CAY-AAY-CAY, AAY-AAY-AAY-AAY-AAY-CAY, CAY-AAY-


 


AAY-AAY-AAY-AAY, AAY-CAY-AAY-AAY-AAY-AAY, AAY-AAY-


 


CAY-AAY-AAY-AAY, AAY-AAY-AAY-CAY-AAY-AAY, AAY-AAY-


 


AAY-AAY-CAY-AAY, AAY-AAY-AAY-AAY-CAY-CAY, CAY-CAY-


 


AAY-AAY-AAY-AAY, CAY-AAY-CAY-AAY-AAY-AAY, CAY-AAY-


 


AAY-CAY-AAY-AAY, CAY-AAY-AAY-AAY-CAY-AAY, CAY-AAY-


 


AAY-AAY-AAY-CAY, AAY-CAY-CAY-AAY-AAY-AAY, AAY-CAY-


 


AAY-CAY-AAY-AAY, AAY-CAY-AAY-AAY-CAY-AAY, AAY-CAY-


 


AAY-AAY-AAY-CAY, AAY-AAY-CAY-CAY-AAY-AAY, AAY-AAY-


 


CAY-AAY-CAY-AAY, AAY-AAY-CAY-AAY-AAY-CAY, AAY-AAY-


 


AAY-CAY-CAY-AAY, AAY-AAY-AAY-CAY-AAY-CAY, AAY-AAY-


 


AAY-AAY-CAY-CAY-CAY, CAY-CAY-CAY-AAY-AAY-AAY-AAY, 


 


CAY-AAY-CAY-CAY-AAY-AAY-AAY, CAY-AAY-CAY-AAY-CAY-


 


AAY-AAY, CAY-AAY-CAY-AAY-AAY-CAY-AAY, CAY-AAY-CAY-


 


AAY-AAY-AAY-CAY, CAY-AAY-AAY-CAY-CAY-AAY-AAY, CAY-


 


AAY-AAY-CAY-AAY-CAY-AAY, CAY-AAY-AAY-CAY-AAY-AAY-


 


CAY, CAY-AAY-AAY-AAY-CAY-AAY-CAY, CAY-AAY-AAY-AAY-


 


CAY-CAY-AAY, CAY-AAY-AAY-AAY-AAY-CAY-CAY, CAY-CAY-


 


AAY-CAY-AAY-AAY-AAY, CAY-CAY-AAY-AAY-CAY-AAY-AAY, 


 


CAY-CAY-AAY-AAY-AAY-CAY-AAY, CAY-CAY-AAY-AAY-AAY-


 


AAY-CAY, AAY-CAY-CAY-CAY-AAY-AAY-AAY, AAY-CAY-CAY-


 


AAY-CAY-AAY-AAY, AAY-CAY-CAY-AAY-AAY-CAY-AAY, AAY-


 


CAY-CAY-AAY-AAY-AAY-CAY, AAY-CAY-AAY-CAY-CAY-AAY-


 


AAY, AAY-CAY-AAY-AAY-CAY-CAY-AAY, AAY-CAY-AAY-AAY-


 


AAY-CAY-CAY, AAY-CAY-AAY-CAY-AAY-CAY-AAY, AAY-CAY-


 


AAY-CAY-AAY-AAY-CAY, AAY-CAY-AAY-AAY-CAY-AAY-CAY, 


 


AAY-AAY-CAY-CAY-CAY-AAY-AAY, AAY-AAY-CAY-CAY-AAY-


 


CAY-AAY, AAY-AAY-CAY-CAY-AAY-AAY-CAY, AAY-AAY-CAY-


 


AAY-CAY-CAY-AAY, AAY-AAY-CAY-AAY-CAY-AAY-CAY, AAY-


 


AAY-CAY-AAY-AAY-CAY-CAY, AAY-AAY-AAY-CAY-CAY-CAY-


 


AAY, AAY-AAY-AAY-CAY-CAY-AAY-CAY, AAY-AAY-AAY-CAY-


 


AAY-CAY-CAY, AAY-AAY-AAY-AAY-AAY-CAY-CAY, CAY-CAY-


 


AAY-AAY-AAY-AAY-AAY, CAY-AAY-CAY-AAY-AAY-AAY-AAY, 


 


CAY-AAY-AAY-CAY-AAY-AAY-AAY, CAY-AAY-AAY-AAY-CAY-


 


AAY-AAY, CAY-AAY-AAY-AAY-AAY-CAY-AAY, CAY-AAY-AAY-


 


AAY-AAY-AAY-CAY, AAY-CAY-CAY-AAY-AAY-AAY-AAY, AAY-


 


CAY-AAY-CAY-AAY-AAY-AAY, AAY-CAY-AAY-AAY-CAY-AAY-


 


AAY, AAY-CAY-AAY-AAY-AAY-CAY-AAY, AAY-CAY-AAY-AAY-


 


AAY-AAY-CAY, AAY-AAY-CAY-CAY-AAY-AAY-AAY, AAY-AAY-


 


CAY-AAY-CAY-AAY-AAY, AAY-AAY-CAY-AAY-AAY-CAY-AAY, 


 


AAY-AAY-CAY-AAY-AAY-AAY-CAY, AAY-AAY-AAY-CAY-CAY-


 


AAY-AAY, AAY-AAY-AAY-CAY-AAY-CAY-AAY, AAY-AAY-AAY-


 


CAY-AAY-AAY-CAY, AAY-AAY-AAY-AAY-CAY-CAY-AAY, AAY-


 


AAY-AAY-AAY-CAY-AAY-CAY-AAY-AAY-AAY-AAY-AAY-AAY-


 


CAY, CAY-AAY-AAY-AAY-AAY-AAY-AAY, AAY-CAY-AAY-AAY-


 


AAY-AAY-AAY, AAY-AAY-CAY-AAY-AAY-AAY-AAY, AAY-AAY-


 


AAY-CAY-AAY-AAY-AAY, AAY-AAY-AAY-AAY-CAY-AAY-AAY, 


 


AAY-AAY-AAY-AAY-AAY-CAY-AAY


 


Oligonucleotides of peptide motifs containing 3-7


amino acid residues with


N(Asparagine) as the major constituent and


D(Aspartic Acid) as the minor constituent


AAY-AAY-GAY, GAY-AAY-AAY, AAY-GAY-AAY, AAY-AAY-AAY-


 


GAY, GAY-AAY-AAY-AAY, AAY-GAY-AAY-AAY, AAY-AAY-GAY-


 


AAY, AAY-AAY-AAY-AAY-GAY, GAY-AAY-AAY-AAY-AAY, AAY-


 


GAY-AAY-AAY-AAY, AAY-AAY-GAY-AAY-AAY, AAY-AAY-AAY-


 


GAY-AAY, AAY-AAY-AAY-GAY-GAY, GAY-GAY-AAY-AAY-AAY, 


 


GAY-AAY-GAY-AAY-AAY, GAY-AAY-AAY-GAY-AAY, GAY-AAY-


 


AAY-AAY-GAY, AAY-GAY-GAY-AAY-AAY, AAY-GAY-AAY-GAY-


 


AAY, AAY-GAY-AAY-AAY-GAY, AAY-AAY-GAY-GAY-AAY, AAY-


 


AAY-GAY-AAY-GAY, AAY-AAY-AAY-AAY-AAY-GAY, GAY-AAY-


 


AAY-AAY-AAY-AAY, AAY-GAY-AAY-AAY-AAY-AAY, AAY-AAY-


 


GAY-AAY-AAY-AAY, AAY-AAY-AAY-GAY-AAY-AAY, AAY-AAY-


 


AAY-AAY-GAY-AAY, AAY-AAY-AAY-AAY-GAY-GAY, GAY-GAY-


 


AAY-AAY-AAY-AAY, GAY-AAY-GAY-AAY-AAY-AAY, GAY-AAY-


 


AAY-GAY-AAY-AAY, GAY-AAY-AAY-AAY-GAY-AAY, GAY-AAY-


 


AAY-AAY-AAY-GAY, AAY-GAY-GAY-AAY-AAY-AAY, AAY-GAY-


 


AAY-GAY-AAY-AAY, AAY-GAY-AAY-AAY-GAY-AAY, AAY-GAY-


 


AAY-AAY-AAY-GAY, AAY-AAY-GAY-GAY-AAY-AAY, AAY-AAY-


 


GAY-AAY-GAY-AAY, AAY-AAY-GAY-AAY-AAY-GAY, AAY-AAY-


 


AAY-GAY-GAY-AAY, AAY-AAY-AAY-GAY-AAY-GAY, AAY-AAY-


 


AAY-AAY-GAY-GAY-GAY, GAY-GAY-GAY-AAY-AAY-AAY-AAY, 


 


GAY-AAY-GAY-GAY-AAY-AAY-AAY, GAY-AAY-GAY-AAY-GAY-


 


AAY-AAY, GAY-AAY-GAY-AAY-AAY-GAY-AAY, GAY-AAY-GAY-


 


AAY-AAY-AAY-GAY, GAY-AAY-AAY-GAY-GAY-AAY-AAY, GAY-


 


AAY-AAY-GAY-AAY-GAY-AAY, GAY-AAY-AAY-GAY-AAY-AAY-


 


GAY, GAY-AAY-AAY-AAY-GAY-AAY-GAY, GAY-AAY-AAY-AAY-


 


GAY-GAY-AAY, GAY-AAY-AAY-AAY-AAY-GAY-GAY, GAY-GAY-


 


AAY-GAY-AAY-AAY-AAY, GAY-GAY-AAY-AAY-GAY-AAY-AAY, 


 


GAY-GAY-AAY-AAY-AAY-GAY-AAY, GAY-GAY-AAY-AAY-AAY-


 


AAY-GAY, AAY-GAY-GAY-GAY-AAY-AAY-AAY, AAY-GAY-GAY-


 


AAY-GAY-AAY-AAY, AAY-GAY-GAY-AAY-AAY-GAY-AAY, AAY-


 


GAY-GAY-AAY-AAY-AAY-GAY, AAY-GAY-AAY-GAY-GAY-AAY-


 


AAY, AAY-GAY-AAY-AAY-GAY-GAY-AAY, AAY-GAY-AAY-AAY-


 


AAY-GAY-GAY, AAY-GAY-AAY-GAY-AAY-GAY-AAY, AAY-GAY-


 


AAY-GAY-AAY-AAY-GAY, AAY-GAY-AAY-AAY-GAY-AAY-GAY, 


 


AAY-AAY-GAY-GAY-GAY-AAY-AAY, AAY-AAY-GAY-GAY-AAY-


 


GAY-AAY, AAY-AAY-GAY-GAY-AAY-AAY-GAY, AAY-AAY-GAY-


 


AAY-GAY-GAY-AAY, AAY-AAY-GAY-AAY-GAY-AAY-GAY, AAY-


 


AAY-GAY-AAY-AAY-GAY-GAY, AAY-AAY-AAY-GAY-GAY-GAY-


 


AAY, AAY-AAY-AAY-GAY-GAY-AAY-GAY, AAY-AAY-AAY-GAY-


 


AAY-GAY-GAY, AAY-AAY-AAY-AAY-AAY-GAY-GAY, GAY-GAY-


 


AAY-AAY-AAY-AAY-AAY, GAY-AAY-GAY-AAY-AAY-AAY-AAY, 


 


GAY-AAY-AAY-GAY-AAY-AAY-AAY, GAY-AAY-AAY-AAY-GAY-


 


AAY-AAY, GAY-AAY-AAY-AAY-AAY-GAY-AAY, GAY-AAY-AAY-


 


AAY-AAY-AAY-GAY, AAY-GAY-GAY-AAY-AAY-AAY-AAY, AAY-


 


GAY-AAY-GAY-AAY-AAY-AAY, AAY-GAY-AAY-AAY-GAY-AAY-


 


AAY, AAY-GAY-AAY-AAY-AAY-GAY-AAY, AAY-GAY-AAY-AAY-


 


AAY-AAY-GAY, AAY-AAY-GAY-GAY-AAY-AAY-AAY, AAY-AAY-


 


GAY-AAY-GAY-AAY-AAY, AAY-AAY-GAY-AAY-AAY-GAY-AAY, 


 


AAY-AAY-GAY-AAY-AAY-AAY-GAY, AAY-AAY-AAY-GAY-GAY-


 


AAY-AAY, AAY-AAY-AAY-GAY-AAY-GAY-AAY, AAY-AAY-AAY-


 


GAY-AAY-AAY-GAY, AAY-AAY-AAY-AAY-GAY-GAY-AAY, AAY-


 


AAY-AAY-AAY-GAY-AAY-GAY-AAY-AAY-AAY-AAY-AAY-AAY-GAY, 


 


GAY-AAY-AAY-AAY-AAY-AAY-AAY, AAY-GAY-AAY-AAY-AAY-


 


AAY-AAY, AAY-AAY-GAY-AAY-AAY-AAY-AAY, AAY-AAY-AAY-


 


GAY-AAY-AAY-AAY, AAY-AAY-AAY-AAY-GAY-AAY-AAY, AAY-


 


AAY-AAY-AAY-AAY-GAY-AAY


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with G


(glycine) as the major constituent and T(Threonine)


as the minor constituent


GGN-GGN-ACN, ACN-GGN-GGN, GGN-ACN-GGN, GGN-GGN-GGN-


 


ACN, ACN-GGN-GGN-GGN, GGN-ACN-GGN-GGN, GGN-GGN-ACN-


 


GGN, GGN-GGN-GGN-GGN-ACN, ACN-GGN-GGN-GGN-GGN, GGN-


 


ACN-GGN-GGN-GGN, GGN-GGN-ACN-GGN-GGN, GGN-GGN-GGN-


 


ACN-GGN, GGN-GGN-GGN-ACN-ACN, ACN-ACN-GGN-GGN-GGN, 


 


ACN-GGN-ACN-GGN-GGN, ACN-GGN-GGN-ACN-GGN, ACN-GGN-


 


GGN-GGN-ACN, GGN-ACN-ACN-GGN-GGN, GGN-ACN-GGN-ACN-


 


GGN, GGN-ACN-GGN-GGN-ACN, GGN-GGN-ACN-ACN-GGN, GGN-


 


GGN-ACN-GGN-ACN, GGN-GGN-GGN-GGN-GGN-ACN, ACN-GGN-


 


GGN-GGN-GGN-GGN, GGN-ACN-GGN-GGN-GGN-GGN, GGN-GGN-


 


ACN-GGN-GGN-GGN, GGN-GGN-GGN-ACN-GGN-GGN, GGN-GGN-


 


GGN-GGN-ACN-GGN, GGN-GGN-GGN-GGN-ACN-ACN, ACN-ACN-


 


GGN-GGN-GGN-GGN, ACN-GGN-ACN-GGN-GGN-GGN, ACN-GGN-


 


GGN-ACN-GGN-GGN, ACN-GGN-GGN-GGN-ACN-GGN, ACN-GGN-


 


GGN-GGN-GGN-ACN, GGN-ACN-ACN-GGN-GGN-GGN, GGN-ACN-


 


GGN-ACN-GGN-GGN, GGN-ACN-GGN-GGN-ACN-GGN, GGN-ACN-


 


GGN-GGN-GGN-ACN, GGN-GGN-ACN-ACN-GGN-GGN, GGN-GGN-


 


ACN-GGN-ACN-GGN, GGN-GGN-ACN-GGN-GGN-ACN, GGN-GGN-


 


GGN-ACN-ACN-GGN, GGN-GGN-GGN-ACN-GGN-ACN, GGN-GGN-


 


GGN-GGN-ACN-ACN-ACN, ACN-ACN-ACN-GGN-GGN-GGN-GGN, 


 


ACN-GGN-ACN-ACN-GGN-GGN-GGN, ACN-GGN-ACN-GGN-ACN-


 


GGN-GGN, ACN-GGN-ACN-GGN-GGN-ACN-GGN, ACN-GGN-ACN-


 


GGN-GGN-GGN-ACN, ACN-GGN-GGN-ACN-ACN-GGN-GGN, ACN-


 


GGN-GGN-ACN-GGN-ACN-GGN, ACN-GGN-GGN-ACN-GGN-GGN-


 


ACN, ACN-GGN-GGN-GGN-ACN-GGN-ACN, ACN-GGN-GGN-GGN-


 


ACN-ACN-GGN, ACN-GGN-GGN-GGN-GGN-ACN-ACN, ACN-ACN-


 


GGN-ACN-GGN-GGN-GGN, ACN-ACN-GGN-GGN-ACN-GGN-GGN, 


 


ACN-ACN-GGN-GGN-GGN-ACN-GGN, ACN-ACN-GGN-GGN-GGN-


 


GGN-ACN, GGN-ACN-ACN-ACN-GGN-GGN-GGN, GGN-ACN-ACN-


 


GGN-ACN-GGN-GGN, GGN-ACN-ACN-GGN-GGN-ACN-GGN, GGN-


 


ACN-ACN-GGN-GGN-GGN-ACN, GGN-ACN-GGN-ACN-ACN-GGN-


 


GGN, GGN-ACN-GGN-GGN-ACN-ACN-GGN, GGN-ACN-GGN-GGN-


 


GGN-ACN-ACN, GGN-ACN-GGN-ACN-GGN-ACN-GGN, GGN-ACN-


 


GGN-ACN-GGN-GGN-ACN, GGN-ACN-GGN-GGN-ACN-GGN-ACN, 


 


GGN-GGN-ACN-ACN-ACN-GGN-GGN, GGN-GGN-ACN-ACN-GGN-


 


ACN-GGN, GGN-GGN-ACN-ACN-GGN-GGN-ACN, GGN-GGN-ACN-


 


GGN-ACN-ACN-GGN, GGN-GGN-ACN-GGN-ACN-GGN-ACN, GGN-


 


GGN-ACN-GGN-GGN-ACN-ACN, GGN-GGN-GGN-ACN-ACN-ACN-


 


GGN, GGN-GGN-GGN-ACN-ACN-GGN-ACN, GGN-GGN-GGN-ACN-


 


GGN-ACN-ACN, GGN-GGN-GGN-GGN-GGN-ACN-ACN, ACN-ACN-


 


GGN-GGN-GGN-GGN-GGN, ACN-GGN-ACN-GGN-GGN-GGN-GGN, 


 


ACN-GGN-GGN-ACN-GGN-GGN-GGN, ACN-GGN-GGN-GGN-ACN-


 


GGN-GGN, ACN-GGN-GGN-GGN-GGN-ACN-GGN, ACN-GGN-GGN-


 


GGN-GGN-GGN-ACN, GGN-ACN-ACN-GGN-GGN-GGN-GGN, GGN-


 


ACN-GGN-ACN-GGN-GGN-GGN, GGN-ACN-GGN-GGN-ACN-GGN-


 


GGN, GGN-ACN-GGN-GGN-GGN-ACN-GGN, GGN-ACN-GGN-GGN-


 


GGN-GGN-ACN, GGN-GGN-ACN-ACN-GGN-GGN-GGN, GGN-GGN-


 


ACN-GGN-ACN-GGN-GGN, GGN-GGN-ACN-GGN-GGN-ACN-GGN, 


 


GGN-GGN-ACN-GGN-GGN-GGN-ACN, GGN-GGN-GGN-ACN-ACN-


 


GGN-GGN, GGN-GGN-GGN-ACN-GGN-ACN-GGN, GGN-GGN-GGN-


 


ACN-GGN-GGN-ACN, GGN-GGN-GGN-GGN-ACN-ACN-GGN, GGN-


 


GGN-GGN-GGN-ACN-GGN-ACN-GGN-GGN-GGN-GGN-GGN-GGN-


 


ACN, ACN-GGN-GGN-GGN-GGN-GGN-GGN, GGN-ACN-GGN-GGN-


 


GGN-GGN-GGN, GGN-GGN-ACN-GGN-GGN-GGN-GGN, GGN-GGN-


 


GGN-ACN-GGN-GGN-GGN, GGN-GGN-GGN-GGN-ACN-GGN-GGN, 


 


GGN-GGN-GGN-GGN-GGN-ACN-GGN


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


G(glycine) as the major constituent and A(Alanine)


as the minor constituent


GGN-GGN-GCN, GCN-GGN-GGN, GGN-GCN-GGN, GGN-GGN-GGN-


 


GCN, GCN-GGN-GGN-GGN, GGN-GCN-GGN-GGN, GGN-GGN-GCN-


 


GGN, GGN-GGN-GGN-GGN-GCN, GCN-GGN-GGN-GGN-GGN, GGN-


 


GCN-GGN-GGN-GGN, GGN-GGN-GCN-GGN-GGN, GGN-GGN-GGN-


 


GCN-GGN, GGN-GGN-GGN-GCN-GCN, GCN-GCN-GGN-GGN-GGN, 


 


GCN-GGN-GCN-GGN-GGN, GCN-GGN-GGN-GCN-GGN, GCN-GGN-


 


GGN-GGN-GCN, GGN-GCN-GCN-GGN-GGN, GGN-GCN-GGN-GCN-


 


GGN, GGN-GCN-GGN-GGN-GCN, GGN-GGN-GCN-GCN-GGN, GGN-


 


GGN-GCN-GGN-GCN, GGN-GGN-GGN-GGN-GGN-GCN, GCN-GGN-


 


GGN-GGN-GGN-GGN, GGN-GCN-GGN-GGN-GGN-GGN, GGN-GGN-


 


GCN-GGN-GGN-GGN, GGN-GGN-GGN-GCN-GGN-GGN, GGN-GGN-


 


GGN-GGN-GCN-GGN, GGN-GGN-GGN-GGN-GCN-GCN, GCN-GCN-


 


GGN-GGN-GGN-GGN, GCN-GGN-GCN-GGN-GGN-GGN, GCN-GGN-


 


GGN-GCN-GGN-GGN, GCN-GGN-GGN-GGN-GCN-GGN, GCN-GGN-


 


GGN-GGN-GGN-GCN, GGN-GCN-GCN-GGN-GGN-GGN, GGN-GCN-


 


GGN-GCN-GGN-GGN, GGN-GCN-GGN-GGN-GCN-GGN, GGN-GCN-


 


GGN-GGN-GGN-GCN, GGN-GGN-GCN-GCN-GGN-GGN, GGN-GGN-


 


GCN-GGN-GCN-GGN, GGN-GGN-GCN-GGN-GGN-GCN, GGN-GGN-


 


GGN-GCN-GCN-GGN, GGN-GGN-GGN-GCN-GGN-GCN, GGN-GGN-


 


GGN-GGN-GCN-GCN-GCN, GCN-GCN-GCN-GGN-GGN-GGN-GGN, 


 


GCN-GGN-GCN-GCN-GGN-GGN-GGN, GCN-GGN-GCN-GGN-GCN-


 


GGN-GGN, GCN-GGN-GCN-GGN-GGN-GCN-GGN, GCN-GGN-GCN-


 


GGN-GGN-GGN-GCN, GCN-GGN-GGN-GCN-GCN-GGN-GGN, GCN-


 


GGN-GGN-GCN-GGN-GCN-GGN, GCN-GGN-GGN-GCN-GGN-GGN-


 


GCN, GCN-GGN-GGN-GGN-GCN-GGN-GCN, GCN-GGN-GGN-GGN-


 


GCN-GCN-GGN, GCN-GGN-GGN-GGN-GGN-GCN-GCN, GCN-GCN-


 


GGN-GCN-GGN-GGN-GGN, GCN-GCN-GGN-GGN-GCN-GGN-GGN, 


 


GCN-GCN-GGN-GGN-GGN-GCN-GGN, GCN-GCN-GGN-GGN-GGN-


 


GGN-GCN, GGN-GCN-GCN-GCN-GGN-GGN-GGN, GGN-GCN-GCN-


 


GGN, GGN-GCN-GCN-GGN-GGN-GCN-GGN, GGN-GCN-GCN-GGN-


 


GGN-GCN-GGN-GGN-GGN-GCN, GGN-GCN-GGN-GCN-GCN-GGN-


 


GGN, GGN-GCN-GGN-GGN-GCN-GCN-GGN, GGN-GCN-GGN-GGN-


 


GGN-GCN-GCN, GGN-GCN-GGN-GCN-GGN-GCN-GGN, GGN-GCN-


 


GGN-GCN-GGN-GGN-GCN, GGN-GCN-GGN-GGN-GCN-GGN-GCN, 


 


GGN-GGN-GCN-GCN-GCN-GGN-GGN, GGN-GGN-GCN-GCN-GGN-


 


GCN-GGN, GGN-GGN-GCN-GCN-GGN-GGN-GCN, GGN-GGN-GCN-


 


GGN-GCN-GCN-GGN, GGN-GGN-GCN-GGN-GCN-GGN-GCN, GGN-


 


GGN-GCN-GGN-GGN-GCN-GCN, GGN-GGN-GGN-GCN-GCN-GCN-


 


GGN, GGN-GGN-GGN-GCN-GCN-GGN-GCN, GGN-GGN-GGN-GCN-


 


GGN-GCN-GCN, GGN-GGN-GGN-GGN-GGN-GCN-GCN, GCN-GCN-


 


GGN-GGN-GGN-GGN-GGN, GCN-GGN-GCN-GGN-GGN-GGN-GGN, 


 


GCN-GGN-GGN-GCN-GGN-GGN-GGN, GCN-GGN-GGN-GGN-GCN-


 


GGN-GGN, GCN-GGN-GGN-GGN-GGN-GCN-GGN, GCN-GGN-GGN-


 


GGN-GGN-GGN-GCN, GGN-GCN-GCN-GGN-GGN-GGN-GGN, GGN-


 


GCN-GGN-GCN-GGN-GGN-GGN, GGN-GCN-GGN-GGN-GCN-GGN-


 


GGN, GGN-GCN-GGN-GGN-GGN-GCN-GGN, GGN-GCN-GGN-GGN-


 


GGN-GGN-GCN, GGN-GGN-GCN-GCN-GGN-GGN-GGN, GGN-GGN-


 


GCN-GGN-GCN-GGN-GGN, GGN-GGN-GCN-GGN-GGN-GCN-GGN, 


 


GGN-GGN-GCN-GGN-GGN-GGN-GCN, GGN-GGN-GGN-GCN-GCN-


 


GGN-GGN, GGN-GGN-GGN-GCN-GGN-GCN-GGN, GGN-GGN-GGN-


 


GCN-GGN-GGN-GCN, GGN-GGN-GGN-GGN-GCN-GCN-GGN, GGN-


 


GGN-GGN-GGN-GCN-GGN-GCN-GGN-GGN-GGN-GGN-GGN-GGN-GCN, 


 


GCN-GGN-GGN-GGN-GGN-GGN-GGN, GGN-GCN-GGN-GGN-GGN-


 


GGN-GGN, GGN-GGN-GCN-GGN-GGN-GGN-GGN, GGN-GGN-GGN-


 


GCN-GGN-GGN-GGN, GGN-GGN-GGN-GGN-GCN-GGN-GGN, GGN-


 


GGN-GGN-GGN-GGN-GCN-GGN


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


G(glycine) as the major constituent and S(Serine)


as the minor constituent


GGN-GGN-AGY, AGY-GGN-GGN, GGN-AGY-GGN, GGN-GGN-GGN-


 


AGY, AGY-GGN-GGN-GGN, GGN-AGY-GGN-GGN, GGN-GGN-AGY-


 


GGN, GGN-GGN-GGN-GGN-AGY, AGY-GGN-GGN-GGN-GGN, GGN-


 


AGY-GGN-GGN-GGN, GGN-GGN-AGY-GGN-GGN, GGN-GGN-GGN-


 


AGY-GGN, GGN-GGN-GGN-AGY-AGY, AGY-AGY-GGN-GGN-GGN, 


 


AGY-GGN-AGY-GGN-GGN, AGY-GGN-GGN-AGY-GGN, AGY-GGN-


 


GGN-GGN-AGY, GGN-AGY-AGY-GGN-GGN, GGN-AGY-GGN-AGY-


 


GGN, GGN-AGY-GGN-GGN-AGY, GGN-GGN-AGY-AGY-GGN, GGN-


 


GGN-AGY-GGN-AGY, GGN-GGN-GGN-GGN-GGN-AGY, AGY-GGN-


 


GGN-GGN-GGN-GGN, GGN-AGY-GGN-GGN-GGN-GGN, GGN-GGN-


 


AGY-GGN-GGN-GGN, GGN-GGN-GGN-AGY-GGN-GGN, GGN-GGN-


 


GGN-GGN-AGY-GGN, GGN-GGN-GGN-GGN-AGY-AGY, AGY-AGY-


 


GGN-GGN-GGN-GGN, AGY-GGN-AGY-GGN-GGN-GGN, AGY-GGN-


 


GGN-AGY-GGN-GGN, AGY-GGN-GGN-GGN-AGY-GGN, AGY-GGN-


 


GGN-GGN-GGN-AGY, GGN-AGY-AGY-GGN-GGN-GGN, GGN-AGY-


 


GGN-AGY-GGN-GGN, GGN-AGY-GGN-GGN-AGY-GGN, GGN-AGY-


 


GGN-GGN-GGN-AGY, GGN-GGN-AGY-AGY-GGN-GGN, GGN-GGN-


 


AGY-GGN-AGY-GGN, GGN-GGN-AGY-GGN-GGN-AGY, GGN-GGN-


 


GGN-AGY-AGY-GGN, GGN-GGN-GGN-AGY-GGN-AGY, GGN-GGN-


 


GGN-GGN-AGY-AGY-AGY, AGY-AGY-AGY-GGN-GGN-GGN-GGN, 


 


AGY-GGN-AGY-AGY-GGN-GGN-GGN, AGY-GGN-AGY-GGN-AGY-


 


GGN-GGN, AGY-GGN-AGY-GGN-GGN-AGY-GGN, AGY-GGN-AGY-


 


GGN-GGN-GGN-AGY, AGY-GGN-GGN-AGY-AGY-GGN-GGN, AGY-


 


GGN-GGN-AGY-GGN-AGY-GGN, AGY-GGN-GGN-AGY-GGN-GGN-


 


AGY, AGY-GGN-GGN-GGN-AGY-GGN-AGY, AGY-GGN-GGN-GGN-


 


AGY-AGY-GGN, AGY-GGN-GGN-GGN-GGN-AGY-AGY, AGY-AGY-


 


GGN-AGY-GGN-GGN-GGN, AGY-AGY-GGN-GGN-AGY-GGN-GGN, 


 


AGY-AGY-GGN-GGN-GGN-AGY-GGN, AGY-AGY-GGN-GGN-GGN-


 


GGN-AGY, GGN-AGY-AGY-AGY-GGN-GGN-GGN, GGN-AGY-AGY-


 


GGN-AGY-GGN-GGN, GGN-AGY-AGY-GGN-GGN-AGY-GGN, GGN-


 


AGY-AGY-GGN-GGN-GGN-AGY, GGN-AGY-GGN-AGY-AGY-GGN-


 


GGN, GGN-AGY-GGN-GGN-AGY-AGY-GGN, GGN-AGY-GGN-GGN-


 


GGN-AGY-AGY, GGN-AGY-GGN-AGY-GGN-AGY-GGN, GGN-AGY-


 


GGN-AGY-GGN-GGN-AGY, GGN-AGY-GGN-GGN-AGY-GGN-AGY, 


 


GGN-GGN-AGY-AGY-AGY-GGN-GGN, GGN-GGN-AGY-AGY-GGN-


 


AGY-GGN, GGN-GGN-AGY-AGY-GGN-GGN-AGY, GGN-GGN-AGY-


 


GGN-AGY-AGY-GGN, GGN-GGN-AGY-GGN-AGY-GGN-AGY, GGN-


 


GGN-AGY-GGN-GGN-AGY-AGY, GGN-GGN-GGN-AGY-AGY-AGY-


 


GGN, GGN-GGN-GGN-AGY-AGY-GGN-AGY, GGN-GGN-GGN-AGY-


 


GGN-AGY-AGY, GGN-GGN-GGN-GGN-GGN-AGY-AGY, AGY-AGY-


 


GGN-GGN-GGN-GGN-GGN, AGY-GGN-AGY-GGN-GGN-GGN-GGN, 


 


AGY-GGN-GGN-AGY-GGN-GGN-GGN, AGY-GGN-GGN-GGN-AGY-


 


GGN-GGN, AGY-GGN-GGN-GGN-GGN-AGY-GGN, AGY-GGN-GGN-


 


GGN-GGN-GGN-AGY, GGN-AGY-AGY-GGN-GGN-GGN-GGN, GGN-


 


AGY-GGN-AGY-GGN-GGN-GGN, GGN-AGY-GGN-GGN-AGY-GGN-


 


GGN, GGN-AGY-GGN-GGN-GGN-AGY-GGN, GGN-AGY-GGN-GGN-


 


GGN-GGN-AGY, GGN-GGN-AGY-AGY-GGN-GGN-GGN, GGN-GGN-


 


AGY-GGN-AGY-GGN-GGN, GGN-GGN-AGY-GGN-GGN-AGY-GGN, 


 


GGN-GGN-AGY-GGN-GGN-GGN-AGY, GGN-GGN-GGN-AGY-AGY-


 


GGN-GGN, GGN-GGN-GGN-AGY-GGN-AGY-GGN, GGN-GGN-GGN-


 


AGY-GGN-GGN-AGY, GGN-GGN-GGN-GGN-AGY-AGY-GGN, GGN-


 


GGN-GGN-GGN-AGY-GGN-AGY-GGN-GGN-GGN-GGN-GGN-GGN-


 


AGY, AGY-GGN-GGN-GGN-GGN-GGN-GGN, GGN-AGY-GGN-GGN-


 


GGN-GGN-GGN, GGN-GGN-AGY-GGN-GGN-GGN-GGN, GGN-GGN-


 


GGN-AGY-GGN-GGN-GGN, GGN-GGN-GGN-GGN-AGY-GGN-GGN, 


 


GGN-GGN-GGN-GGN-GGN-AGY-GGN


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


G(glycine) as the major constituent and


Q(Glutamine) as the minor constituent


GGN-GGN-CAR, CAR-GGN-GGN, GGN-CAR-GGN, GGN-GGN-GGN-


 


CAR, CAR-GGN-GGN-GGN, GGN-CAR-GGN-GGN, GGN-GGN-CAR-


 


GGN, GGN-GGN-GGN-GGN-CAR, CAR-GGN-GGN-GGN-GGN, GGN-


 


CAR-GGN-GGN-GGN, GGN-GGN-CAR-GGN-GGN, GGN-GGN-GGN-


 


CAR-GGN, GGN-GGN-GGN-CAR-CAR, CAR-CAR-GGN-GGN-GGN, 


 


CAR-GGN-CAR-GGN-GGN, CAR-GGN-GGN-CAR-GGN, CAR-GGN-


 


GGN-GGN-CAR, GGN-CAR-CAR-GGN-GGN, GGN-CAR-GGN-CAR-


 


GGN, GGN-CAR-GGN-GGN-CAR, GGN-GGN-CAR-CAR-GGN, GGN-


 


GGN-CAR-GGN-CAR, GGN-GGN-GGN-GGN-GGN-CAR, CAR-GGN-


 


GGN-GGN-GGN-GGN, GGN-CAR-GGN-GGN-GGN-GGN, GGN-GGN-


 


CAR-GGN-GGN-GGN, GGN-GGN-GGN-CAR-GGN-GGN, GGN-GGN-


 


GGN-GGN-CAR-GGN, GGN-GGN-GGN-GGN-CAR-CAR, CAR-CAR-


 


GGN-GGN-GGN-GGN, CAR-GGN-CAR-GGN-GGN-GGN, CAR-GGN-


 


GGN-CAR-GGN-GGN, CAR-GGN-GGN-GGN-CAR-GGN, CAR-GGN-


 


GGN-GGN-GGN-CAR, GGN-CAR-CAR-GGN-GGN-GGN, GGN-CAR-


 


GGN-CAR-GGN-GGN, GGN-CAR-GGN-GGN-CAR-GGN, GGN-CAR-


 


GGN-GGN-GGN-CAR, GGN-GGN-CAR-CAR-GGN-GGN, GGN-GGN-


 


CAR-GGN-CAR-GGN, GGN-GGN-CAR-GGN-GGN-CAR, GGN-GGN-


 


GGN-CAR-CAR-GGN, GGN-GGN-GGN-CAR-GGN-CAR, GGN-GGN-


 


GGN-GGN-CAR-CAR-CAR, CAR-CAR-CAR-GGN-GGN-GGN-GGN, 


 


CAR-GGN-CAR-CAR-GGN-GGN-GGN, CAR-GGN-CAR-GGN-CAR-


 


GGN-GGN, CAR-GGN-CAR-GGN-GGN-CAR-GGN, CAR-GGN-CAR-


 


GGN-GGN-GGN-CAR, CAR-GGN-GGN-CAR-CAR-GGN-GGN, CAR-


 


GGN-GGN-CAR-GGN-CAR-GGN, CAR-GGN-GGN-CAR-GGN-GGN-


 


CAR, CAR-GGN-GGN-GGN-CAR-GGN-CAR, CAR-GGN-GGN-GGN-


 


CAR-CAR-GGN, CAR-GGN-GGN-GGN-GGN-CAR-CAR, CAR-CAR-


 


GGN-CAR-GGN-GGN-GGN, CAR-CAR-GGN-GGN-CAR-GGN-GGN, 


 


CAR-CAR-GGN-GGN-GGN-CAR-GGN, CAR-CAR-GGN-GGN-GGN-


 


GGN-CAR, GGN-CAR-CAR-CAR-GGN-GGN-GGN, GGN-CAR-CAR-


 


GGN-CAR-GGN-GGN, GGN-CAR-CAR-GGN-GGN-CAR-GGN, GGN-


 


CAR-CAR-GGN-GGN-GGN-CAR, GGN-CAR-GGN-CAR-CAR-GGN-


 


GGN, GGN-CAR-GGN-GGN-CAR-CAR-GGN, GGN-CAR-GGN-GGN-


 


GGN-CAR-CAR, GGN-CAR-GGN-CAR-GGN-CAR-GGN, GGN-CAR-


 


GGN-CAR-GGN-GGN-CAR, GGN-CAR-GGN-GGN-CAR-GGN-CAR, 


 


GGN-GGN-CAR-CAR-CAR-GGN-GGN, GGN-GGN-CAR-CAR-GGN-


 


CAR-GGN, GGN-GGN-CAR-CAR-GGN-GGN-CAR, GGN-GGN-CAR-


 


GGN-CAR-CAR-GGN, GGN-GGN-CAR-GGN-CAR-GGN-CAR, GGN-


 


GGN-CAR-GGN-GGN-CAR-CAR, GGN-GGN-GGN-CAR-CAR-CAR-


 


GGN, GGN-GGN-GGN-CAR-CAR-GGN-CAR, GGN-GGN-GGN-CAR-


 


GGN-CAR-CAR, GGN-GGN-GGN-GGN-GGN-CAR-CAR, CAR-CAR-


 


GGN-GGN-GGN-GGN-GGN, CAR-GGN-CAR-GGN-GGN-GGN-GGN, 


 


CAR-GGN-GGN-CAR-GGN-GGN-GGN, CAR-GGN-GGN-GGN-CAR-


 


GGN-GGN, CAR-GGN-GGN-GGN-GGN-CAR-GGN, CAR-GGN-GGN-


 


GGN-GGN-GGN-CAR, GGN-CAR-CAR-GGN-GGN-GGN-GGN, GGN-


 


CAR-GGN-CAR-GGN-GGN-GGN, GGN-CAR-GGN-GGN-CAR-GGN-


 


GGN, GGN-CAR-GGN-GGN-GGN-CAR-GGN, GGN-CAR-GGN-GGN-


 


GGN-GGN-CAR, GGN-GGN-CAR-CAR-GGN-GGN-GGN, GGN-GGN-


 


CAR-GGN-CAR-GGN-GGN, GGN-GGN-CAR-GGN-GGN-CAR-GGN, 


 


GGN-GGN-CAR-GGN-GGN-GGN-CAR, GGN-GGN-GGN-CAR-CAR-


 


GGN-GGN, GGN-GGN-GGN-CAR-GGN-CAR-GGN, GGN-GGN-GGN-


 


CAR-GGN-GGN-CAR, GGN-GGN-GGN-GGN-CAR-CAR-GGN, GGN-


 


GGN-GGN-GGN-CAR-GGN-CAR-GGN-GGN-GGN-GGN-GGN-GGN-CAR, 


 


CAR-GGN-GGN-GGN-GGN-GGN-GGN, GGN-CAR-GGN-GGN-GGN-


 


GGN-GGN, GGN-GGN-CAR-GGN-GGN-GGN-GGN, GGN-GGN-GGN-


 


CAR-GGN-GGN-GGN, GGN-GGN-GGN-GGN-CAR-GGN-GGN, GGN-


 


GGN-GGN-GGN-GGN-CAR-GGN


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


G(glycine) as the major constituent and


E(Glutamic Acid) as the minor constituent


GGN-GGN-GAR, GAR-GGN-GGN, GGN-GAR-GGN, GGN-GGN-GGN-


 


GAR, GAR-GGN-GGN-GGN, GGN-GAR-GGN-GGN, GGN-GGN-GAR-


 


GGN, GGN-GGN-GGN-GGN-GAR, GAR-GGN-GGN-GGN-GGN, GGN-


 


GAR-GGN-GGN-GGN, GGN-GGN-GAR-GGN-GGN, GGN-GGN-GGN-


 


GAR-GGN, GGN-GGN-GGN-GAR-GAR, GAR-GAR-GGN-GGN-GGN, 


 


GAR-GGN-GAR-GGN-GGN, GAR-GGN-GGN-GAR-GGN, GAR-GGN-


 


GGN-GGN-GAR, GGN-GAR-GAR-GGN-GGN, GGN-GAR-GGN-GAR-


 


GGN, GGN-GAR-GGN-GGN-GAR, GGN-GGN-GAR-GAR-GGN, GGN-


 


GGN-GAR-GGN-GAR, GGN-GGN-GGN-GGN-GGN-GAR, GAR-GGN-


 


GGN-GGN-GGN-GGN, GGN-GAR-GGN-GGN-GGN-GGN, GGN-GGN-


 


GAR-GGN-GGN-GGN, GGN-GGN-GGN-GAR-GGN-GGN, GGN-GGN-


 


GGN-GGN-GAR-GGN, GGN-GGN-GGN-GGN-GAR-GAR, GAR-GAR-


 


GGN-GGN-GGN-GGN, GAR-GGN-GAR-GGN-GGN-GGN, GAR-GGN-


 


GGN-GAR-GGN-GGN, GAR-GGN-GGN-GGN-GAR-GGN, GAR-GGN-


 


GGN-GGN-GGN-GAR, GGN-GAR-GAR-GGN-GGN-GGN, GGN-GAR-


 


GGN-GAR-GGN-GGN, GGN-GAR-GGN-GGN-GAR-GGN, GGN-GAR-


 


GGN-GGN-GGN-GAR, GGN-GGN-GAR-GAR-GGN-GGN, GGN-GGN-


 


GAR-GGN-GAR-GGN, GGN-GGN-GAR-GGN-GGN-GAR, GGN-GGN-


 


GGN-GAR-GAR-GGN, GGN-GGN-GGN-GAR-GGN-GAR, GGN-GGN-


 


GGN-GGN-GAR-GAR-GAR, GAR-GAR-GAR-GGN-GGN-GGN-GGN, 


 


GAR-GGN-GAR-GAR-GGN-GGN-GGN, GAR-GGN-GAR-GGN-GAR-


 


GGN-GGN, GAR-GGN-GAR-GGN-GGN-GAR-GGN, GAR-GGN-GAR-


 


GGN-GGN-GGN-GAR, GAR-GGN-GGN-GAR-GAR-GGN-GGN, GAR-


 


GGN-GGN-GAR-GGN-GAR-GGN, GAR-GGN-GGN-GAR-GGN-GGN-


 


GAR, GAR-GGN-GGN-GGN-GAR-GGN-GAR, GAR-GGN-GGN-GGN-


 


GAR-GAR-GGN, GAR-GGN-GGN-GGN-GGN-GAR-GAR, GAR-GAR-


 


GGN-GAR-GGN-GGN-GGN, GAR-GAR-GGN-GGN-GAR-GGN-GGN, 


 


GAR-GAR-GGN-GGN-GGN-GAR-GGN, GAR-GAR-GGN-GGN-GGN-


 


GGN-GAR, GGN-GAR-GAR-GAR-GGN-GGN-GGN, GGN-GAR-GAR-


 


GGN-GAR-GGN-GGN, GGN-GAR-GAR-GGN-GGN-GAR-GGN, GGN-


 


GAR-GAR-GGN-GGN-GGN-GAR, GGN-GAR-GGN-GAR-GAR-GGN-


 


GGN, GGN-GAR-GGN-GGN-GAR-GAR-GGN, GGN-GAR-GGN-GGN-


 


GGN-GAR-GAR, GGN-GAR-GGN-GAR-GGN-GAR-GGN, GGN-GAR-


 


GGN-GAR-GGN-GGN-GAR, GGN-GAR-GGN-GGN-GAR-GGN-GAR, 


 


GGN-GGN-GAR-GAR-GAR-GGN-GGN, GGN-GGN-GAR-GAR-GGN-


 


GAR-GGN, GGN-GGN-GAR-GAR-GGN-GGN-GAR, GGN-GGN-GAR-


 


GGN-GAR-GAR-GGN, GGN-GGN-GAR-GGN-GAR-GGN-GAR, GGN-


 


GGN-GAR-GGN-GGN-GAR-GAR, GGN-GGN-GGN-GAR-GAR-GAR-


 


GGN, GGN-GGN-GGN-GAR-GAR-GGN-GAR, GGN-GGN-GGN-GAR-


 


GGN-GAR-GAR, GGN-GGN-GGN-GGN-GGN-GAR-GAR, GAR-GAR-


 


GGN-GGN-GGN-GGN-GGN, GAR-GGN-GAR-GGN-GGN-GGN-GGN, 


 


GAR-GGN-GGN-GAR-GGN-GGN-GGN, GAR-GGN-GGN-GGN-GAR-


 


GGN-GGN, GAR-GGN-GGN-GGN-GGN-GAR-GGN, GAR-GGN-GGN-


 


GGN-GGN-GGN-GAR, GGN-GAR-GAR-GGN-GGN-GGN-GGN, GGN-


 


GAR-GGN-GAR-GGN-GGN-GGN, GGN-GAR-GGN-GGN-GAR-GGN-


 


GGN, GGN-GAR-GGN-GGN-GGN-GAR-GGN, GGN-GAR-GGN-GGN-


 


GGN-GGN-GAR, GGN-GGN-GAR-GAR-GGN-GGN-GGN, GGN-GGN-


 


GAR-GGN-GAR-GGN-GGN, GGN-GGN-GAR-GGN-GGN-GAR-GGN, 


 


GGN-GGN-GAR-GGN-GGN-GGN-GAR, GGN-GGN-GGN-GAR-GAR-


 


GGN-GGN, GGN-GGN-GGN-GAR-GGN-GAR-GGN, GGN-GGN-GGN-


 


GAR-GGN-GGN-GAR, GGN-GGN-GGN-GGN-GAR-GAR-GGN, GGN-


 


GGN-GGN-GGN-GAR-GGN-GAR-GGN-GGN-GGN-GGN-GGN-GGN-GAR, 


 


GAR-GGN-GGN-GGN-GGN-GGN-GGN, GGN-GAR-GGN-GGN-GGN-


 


GGN-GGN, GGN-GGN-GAR-GGN-GGN-GGN-GGN, GGN-GGN-GGN-


 


GAR-GGN-GGN-GGN, GGN-GGN-GGN-GGN-GAR-GGN-GGN, GGN-


 


GGN-GGN-GGN-GGN-GAR-GGN


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


G(glycine) as the major constituent and 


H(Histidine) as the minor constituent


GGN-GGN-CAY, CAY-GGN-GGN, GGN-CAY-GGN, GGN-GGN-GGN-


 


CAY, CAY-GGN-GGN-GGN, GGN-CAY-GGN-GGN, GGN-GGN-CAY-


 


GGN, GGN-GGN-GGN-GGN-CAY, CAY-GGN-GGN-GGN-GGN, GGN-


 


CAY-GGN-GGN-GGN, GGN-GGN-CAY-GGN-GGN, GGN-GGN-GGN-


 


CAY-GGN, GGN-GGN-GGN-CAY-CAY, CAY-CAY-GGN-GGN-GGN, 


 


CAY-GGN-CAY-GGN-GGN, CAY-GGN-GGN-CAY-GGN, CAY-GGN-


 


GGN-GGN-CAY, GGN-CAY-CAY-GGN-GGN, GGN-CAY-GGN-CAY-


 


GGN, GGN-CAY-GGN-GGN-CAY, GGN-GGN-CAY-CAY-GGN, GGN-


 


GGN-CAY-GGN-CAY, GGN-GGN-GGN-GGN-GGN-CAY, CAY-GGN-


 


GGN-GGN-GGN-GGN, GGN-CAY-GGN-GGN-GGN-GGN, GGN-GGN-


 


CAY-GGN-GGN-GGN, GGN-GGN-GGN-CAY-GGN-GGN, GGN-GGN-


 


GGN-GGN-CAY-GGN, GGN-GGN-GGN-GGN-CAY-CAY, CAY-CAY-


 


GGN-GGN-GGN-GGN, CAY-GGN-CAY-GGN-GGN-GGN, CAY-GGN-


 


GGN-CAY-GGN-GGN, CAY-GGN-GGN-GGN-CAY-GGN, CAY-GGN-


 


GGN-GGN-GGN-CAY, GGN-CAY-CAY-GGN-GGN-GGN, GGN-CAY-


 


GGN-CAY-GGN-GGN, GGN-CAY-GGN-GGN-CAY-GGN, GGN-CAY-


 


GGN-GGN-GGN-CAY, GGN-GGN-CAY-CAY-GGN-GGN, GGN-GGN-


 


CAY-GGN-CAY-GGN, GGN-GGN-CAY-GGN-GGN-CAY, GGN-GGN-


 


GGN-CAY-CAY-GGN, GGN-GGN-GGN-CAY-GGN-CAY, GGN-GGN-


 


GGN-GGN-CAY-CAY-CAY, CAY-CAY-CAY-GGN-GGN-GGN-GGN, 


 


CAY-GGN-CAY-CAY-GGN-GGN-GGN, CAY-GGN-CAY-GGN-CAY-


 


GGN-GGN, CAY-GGN-CAY-GGN-GGN-CAY-GGN, CAY-GGN-CAY-


 


GGN-GGN-GGN-CAY, CAY-GGN-GGN-CAY-CAY-GGN-GGN, CAY-


 


GGN-GGN-CAY-GGN-CAY-GGN, CAY-GGN-GGN-CAY-GGN-GGN-


 


CAY, CAY-GGN-GGN-GGN-CAY-GGN-CAY, CAY-GGN-GGN-GGN-


 


CAY-CAY-GGN, CAY-GGN-GGN-GGN-GGN-CAY-CAY, CAY-CAY-


 


GGN-CAY-GGN-GGN-GGN, CAY-CAY-GGN-GGN-CAY-GGN-GGN, 


 


CAY-CAY-GGN-GGN-GGN-CAY-GGN, CAY-CAY-GGN-GGN-GGN-


 


GGN-CAY, GGN-CAY-CAY-CAY-GGN-GGN-GGN, GGN-CAY-CAY-


 


GGN-CAY-GGN-GGN, GGN-CAY-CAY-GGN-GGN-CAY-GGN, GGN-


 


CAY-CAY-GGN-GGN-GGN-CAY, GGN-CAY-GGN-CAY-CAY-GGN-


 


GGN, GGN-CAY-GGN-GGN-CAY-CAY-GGN, GGN-CAY-GGN-GGN-


 


GGN-CAY-CAY, GGN-CAY-GGN-CAY-GGN-CAY-GGN, GGN-CAY-


 


GGN-CAY-GGN-GGN-CAY, GGN-CAY-GGN-GGN-CAY-GGN-CAY, 


 


GGN-GGN-CAY-CAY-CAY-GGN-GGN, GGN-GGN-CAY-CAY-GGN-


 


CAY-GGN, GGN-GGN-CAY-CAY-GGN-GGN-CAY, GGN-GGN-CAY-


 


GGN-CAY-CAY-GGN, GGN-GGN-CAY-GGN-CAY-GGN-CAY, GGN-


 


GGN-CAY-GGN-GGN-CAY-CAY, GGN-GGN-GGN-CAY-CAY-CAY-


 


GGN, GGN-GGN-GGN-CAY-CAY-GGN-CAY, GGN-GGN-GGN-CAY-


 


GGN-CAY-CAY, GGN-GGN-GGN-GGN-GGN-CAY-CAY, CAY-CAY-


 


GGN-GGN-GGN-GGN-GGN, CAY-GGN-CAY-GGN-GGN-GGN-GGN, 


 


CAY-GGN-GGN-CAY-GGN-GGN-GGN, CAY-GGN-GGN-GGN-CAY-


 


GGN-GGN, CAY-GGN-GGN-GGN-GGN-CAY-GGN, CAY-GGN-GGN-


 


GGN-GGN-GGN-CAY, GGN-CAY-CAY-GGN-GGN-GGN-GGN, GGN-


 


CAY-GGN-CAY-GGN-GGN-GGN, GGN-CAY-GGN-GGN-CAY-GGN-


 


GGN, GGN-CAY-GGN-GGN-GGN-CAY-GGN, GGN-CAY-GGN-GGN-


 


GGN-GGN-CAY, GGN-GGN-CAY-CAY-GGN-GGN-GGN, GGN-GGN-


 


CAY-GGN-CAY-GGN-GGN, GGN-GGN-CAY-GGN-GGN-CAY-GGN, 


 


GGN-GGN-CAY-GGN-GGN-GGN-CAY, GGN-GGN-GGN-CAY-CAY-


 


GGN-GGN, GGN-GGN-GGN-CAY-GGN-CAY-GGN, GGN-GGN-GGN-


 


CAY-GGN-GGN-CAY, GGN-GGN-GGN-GGN-CAY-CAY-GGN, GGN-


 


GGN-GGN-GGN-CAY-GGN-CAY-GGN-GGN-GGN-GGN-GGN-GGN-CAY, 


 


CAY-GGN-GGN-GGN-GGN-GGN-GGN, GGN-CAY-GGN-GGN-GGN-


 


GGN-GGN, GGN-GGN-CAY-GGN-GGN-GGN-GGN, GGN-GGN-GGN-


 


CAY-GGN-GGN-GGN, GGN-GGN-GGN-GGN-CAY-GGN-GGN, GGN-


 


GGN-GGN-GGN-GGN-CAY-GGN


 


Oligonucleotides of peptide motifs containing 3-7 amino acide residues with


G(glycine) as the major constituent and N(Asparagine) as the minor constituent


GGN-GGN-AAY, AAY-GGN-GGN, GGN-AAY-GGN, GGN-GGN-GGN-


 


AAY, AAY-GGN-GGN-GGN, GGN-AAY-GGN-GGN, GGN-GGN-AAY-


 


GGN, GGN-GGN-GGN-GGN-AAY, AAY-GGN-GGN-GGN-GGN, GGN-


 


AAY-GGN-GGN-GGN, GGN-GGN-AAY-GGN-GGN, GGN-GGN-GGN-


 


AAY-GGN, GGN-GGN-GGN-AAY-AAY, AAY-AAY-GGN-GGN-GGN, 


 


AAY-GGN-AAY-GGN-GGN, AAY-GGN-GGN-AAY-GGN, AAY-GGN-


 


GGN-GGN-AAY, GGN-AAY-AAY-GGN-GGN, GGN-AAY-GGN-AAY-


 


GGN, GGN-AAY-GGN-GGN-AAY, GGN-GGN-AAY-AAY-GGN, GGN-


 


GGN-AAY-GGN-AAY, GGN-GGN-GGN-GGN-GGN-AAY, AAY-GGN-


 


GGN-GGN-GGN-GGN, GGN-AAY-GGN-GGN-GGN-GGN, GGN-GGN-


 


AAY-GGN-GGN-GGN, GGN-GGN-GGN-AAY-GGN-GGN, GGN-GGN-


 


GGN-GGN-AAY-GGN, GGN-GGN-GGN-GGN-AAY-AAY, AAY-AAY-


 


GGN-GGN-GGN-GGN, AAY-GGN-AAY-GGN-GGN-GGN, AAY-GGN-


 


GGN-AAY-GGN-GGN, AAY-GGN-GGN-GGN-AAY-GGN, AAY-GGN-


 


GGN-GGN-GGN-AAY, GGN-AAY-AAY-GGN-GGN-GGN, GGN-AAY-


 


GGN-AAY-GGN-GGN, GGN-AAY-GGN-GGN-AAY-GGN, GGN-AAY-


 


GGN-GGN-GGN-AAY, GGN-GGN-AAY-AAY-GGN-GGN, GGN-GGN-


 


AAY-GGN-AAY-GGN, GGN-GGN-AAY-GGN-GGN-AAY, GGN-GGN-


 


GGN-AAY-AAY-GGN, GGN-GGN-GGN-AAY-GGN-AAY, GGN-GGN-


 


GGN-GGN-AAY-AAY-AAY, AAY-AAY-AAY-GGN-GGN-GGN-GGN, 


 


AAY-GGN-AAY-AAY-GGN-GGN-GGN, AAY-GGN-AAY-GGN-AAY-


 


GGN-GGN, AAY-GGN-AAY-GGN-GGN-AAY-GGN, AAY-GGN-AAY-


 


GGN-GGN-GGN-AAY, AAY-GGN-GGN-AAY-AAY-GGN-GGN, AAY-


 


GGN-GGN-AAY-GGN-AAY-GGN, AAY-GGN-GGN-AAY-GGN-GGN-


 


AAY, AAY-GGN-GGN-GGN-AAY-GGN-AAY, AAY-GGN-GGN-GGN-


 


AAY-AAY-GGN, AAY-GGN-GGN-GGN-GGN-AAY-AAY, AAY-AAY-


 


GGN-AAY-GGN-GGN-GGN, AAY-AAY-GGN-GGN-AAY-GGN-GGN, 


 


AAY-AAY-GGN-GGN-GGN-AAY-GGN, AAY-AAY-GGN-GGN-GGN-


 


GGN-AAY, GGN-AAY-AAY-AAY-GGN-GGN-GGN, GGN-AAY-AAY-


 


GGN-AAY-GGN-GGN, GGN-AAY-AAY-GGN-GGN-AAY-GGN, GGN-


 


AAY-AAY-GGN-GGN-GGN-AAY, GGN-AAY-GGN-AAY-AAY-GGN-


 


GGN, GGN-AAY-GGN-GGN-AAY-AAY-GGN, GGN-AAY-GGN-GGN-


 


GGN-AAY-AAY, GGN-AAY-GGN-AAY-GGN-AAY-GGN, GGN-AAY-


 


GGN-AAY-GGN-GGN-AAY, GGN-AAY-GGN-GGN-AAY-GGN-AAY, 


 


GGN-GGN-AAY-AAY-AAY-GGN-GGN, GGN-GGN-AAY-AAY-GGN-


 


AAY-GGN, GGN-GGN-AAY-AAY-GGN-GGN-AAY, GGN-GGN-AAY-


 


GGN-AAY-AAY-GGN, GGN-GGN-AAY-GGN-AAY-GGN-AAY, GGN-


 


GGN-AAY-GGN-GGN-AAY-AAY, GGN-GGN-GGN-AAY-AAY-AAY-


 


GGN, GGN-GGN-GGN-AAY-AAY-GGN-AAY, GGN-GGN-GGN-AAY-


 


GGN-AAY-AAY, GGN-GGN-GGN-GGN-GGN-AAY-AAY, AAY-AAY-


 


GGN-GGN-GGN-GGN-GGN, AAY-GGN-AAY-GGN-GGN-GGN-GGN, 


 


AAY-GGN-GGN-AAY-GGN-GGN-GGN, AAY-GGN-GGN-GGN-AAY-


 


GGN-GGN, AAY-GGN-GGN-GGN-GGN-AAY-GGN, AAY-GGN-GGN-


 


GGN-GGN-GGN-AAY, GGN-AAY-AAY-GGN-GGN-GGN-GGN, GGN-


 


AAY-GGN-AAY-GGN-GGN-GGN, GGN-AAY-GGN-GGN-AAY-GGN-


 


GGN, GGN-AAY-GGN-GGN-GGN-AAY-GGN, GGN-AAY-GGN-GGN-


 


GGN-GGN-AAY, GGN-GGN-AAY-AAY-GGN-GGN-GGN, GGN-GGN-


 


AAY-GGN-AAY-GGN-GGN, GGN-GGN-AAY-GGN-GGN-AAY-GGN, 


 


GGN-GGN-AAY-GGN-GGN-GGN-AAY, GGN-GGN-GGN-AAY-AAY-


 


GGN-GGN, GGN-GGN-GGN-AAY-GGN-AAY-GGN, GGN-GGN-GGN-


 


AAY-GGN-GGN-AAY, GGN-GGN-GGN-GGN-AAY-AAY-GGN, GGN-


 


GGN-GGN-GGN-AAY-GGN-AAY-GGN-GGN-GGN-GGN-GGN-GGN-


 


AAY, AAY-GGN-GGN-GGN-GGN-GGN-GGN, GGN-AAY-GGN-GGN-


 


GGN-GGN-GGN, GGN-GGN-AAY-GGN-GGN-GGN-GGN, GGN-GGN-


 


GGN-AAY-GGN-GGN-GGN, GGN-GGN-GGN-GGN-AAY-GGN-GGN, 


 


GGN-GGN-GGN-GGN-GGN-AAY-GGN


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


G(glycine) as the major constituent and 


D(Aspartic Acid) as the minor constituent


GGN-GGN-GAY, GAY-GGN-GGN, GGN-GAY-GGN, GGN-GGN-GGN-


 


GAY, GAY-GGN-GGN-GGN, GGN-GAY-GGN-GGN, GGN-GGN-GAY-


 


GGN, GGN-GGN-GGN-GGN-GAY, GAY-GGN-GGN-GGN-GGN, GGN-


 


GAY-GGN-GGN-GGN, GGN-GGN-GAY-GGN-GGN, GGN-GGN-GGN-


 


GAY-GGN, GGN-GGN-GGN-GAY-GAY, GAY-GAY-GGN-GGN-GGN, 


 


GAY-GGN-GAY-GGN-GGN, GAY-GGN-GGN-GAY-GGN, GAY-GGN-


 


GGN-GGN-GAY, GGN-GAY-GAY-GGN-GGN, GGN-GAY-GGN-GAY-


 


GGN, GGN-GAY-GGN-GGN-GAY, GGN-GGN-GAY-GAY-GGN, GGN-


 


GGN-GAY-GGN-GAY, GGN-GGN-GGN-GGN-GGN-GAY, GAY-GGN-


 


GGN-GGN-GGN-GGN, GGN-GAY-GGN-GGN-GGN-GGN, GGN-GGN-


 


GAY-GGN-GGN-GGN, GGN-GGN-GGN-GAY-GGN-GGN, GGN-GGN-


 


GGN-GGN-GAY-GGN, GGN-GGN-GGN-GGN-GAY-GAY, GAY-GAY-


 


GGN-GGN-GGN-GGN, GAY-GGN-GAY-GGN-GGN-GGN, GAY-GGN-


 


GGN-GAY-GGN-GGN, GAY-GGN-GGN-GGN-GAY-GGN, GAY-GGN-


 


GGN-GGN-GGN-GAY, GGN-GAY-GAY-GGN-GGN-GGN, GGN-GAY-


 


GGN-GAY-GGN-GGN, GGN-GAY-GGN-GGN-GAY-GGN, GGN-GAY-


 


GGN-GGN-GGN-GAY, GGN-GGN-GAY-GAY-GGN-GGN, GGN-GGN-


 


GAY-GGN-GAY-GGN, GGN-GGN-GAY-GGN-GGN-GAY, GGN-GGN-


 


GGN-GAY-GAY-GGN, GGN-GGN-GGN-GAY-GGN-GAY, GGN-GGN-


 


GGN-GGN-GAY-GAY-GAY, GAY-GAY-GAY-GGN-GGN-GGN-GGN, 


 


GAY-GGN-GAY-GAY-GGN-GGN-GGN, GAY-GGN-GAY-GGN-GAY-


 


GGN-GGN, GAY-GGN-GAY-GGN-GGN-GAY-GGN, GAY-GGN-GAY-


 


GGN-GGN-GGN-GAY, GAY-GGN-GGN-GAY-GAY-GGN-GGN, GAY-


 


GGN-GGN-GAY-GGN-GAY-GGN, GAY-GGN-GGN-GAY-GGN-GGN-


 


GAY, GAY-GGN-GGN-GGN-GAY-GGN-GAY, GAY-GGN-GGN-GGN-


 


GAY-GAY-GGN, GAY-GGN-GGN-GGN-GGN-GAY-GAY, GAY-GAY-


 


GGN-GAY-GGN-GGN-GGN, GAY-GAY-GGN-GGN-GAY-GGN-GGN, 


 


GAY-GAY-GGN-GGN-GGN-GAY-GGN, GAY-GAY-GGN-GGN-GGN-


 


GGN-GAY, GGN-GAY-GAY-GAY-GGN-GGN-GGN, GGN-GAY-GAY-


 


GGN-GAY-GGN-GGN, GGN-GAY-GAY-GGN-GGN-GAY-GGN, GGN-


 


GAY-GAY-GGN-GGN-GGN-GAY, GGN-GAY-GGN-GAY-GAY-GGN-


 


GGN, GGN-GAY-GGN-GGN-GAY-GAY-GGN, GGN-GAY-GGN-GGN-


 


GGN-GAY-GAY, GGN-GAY-GGN-GAY-GGN-GAY-GGN, GGN-GAY-


 


GGN-GAY-GGN-GGN-GAY, GGN-GAY-GGN-GGN-GAY-GGN-GAY, 


 


GGN-GGN-GAY-GAY-GAY-GGN-GGN, GGN-GGN-GAY-GAY-GGN-


 


GAY-GGN, GGN-GGN-GAY-GAY-GGN-GGN-GAY, GGN-GGN-GAY-


 


GGN-GAY-GAY-GGN, GGN-GGN-GAY-GGN-GAY-GGN-GAY, GGN-


 


GGN-GAY-GGN-GGN-GAY-GAY, GGN-GGN-GGN-GAY-GAY-GAY-


 


GGN, GGN-GGN-GGN-GAY-GAY-GGN-GAY, GGN-GGN-GGN-GAY-


 


GGN-GAY-GAY, GGN-GGN-GGN-GGN-GGN-GAY-GAY, GAY-GAY-


 


GGN-GGN-GGN-GGN-GGN, GAY-GGN-GAY-GGN-GGN-GGN-GGN, 


 


GAY-GGN-GGN-GAY-GGN-GGN-GGN, GAY-GGN-GGN-GGN-GAY-


 


GGN-GGN, GAY-GGN-GGN-GGN-GGN-GAY-GGN, GAY-GGN-GGN-


 


GGN-GGN-GGN-GAY, GGN-GAY-GAY-GGN-GGN-GGN-GGN, GGN-


 


GAY-GGN-GAY-GGN-GGN-GGN, GGN-GAY-GGN-GGN-GAY-GGN-


 


GGN, GGN-GAY-GGN-GGN-GGN-GAY-GGN, GGN-GAY-GGN-GGN-


 


GGN-GGN-GAY, GGN-GGN-GAY-GAY-GGN-GGN-GGN, GGN-GGN-


 


GAY-GGN-GAY-GGN-GGN, GGN-GGN-GAY-GGN-GGN-GAY-GGN, 


 


GGN-GGN-GAY-GGN-GGN-GGN-GAY, GGN-GGN-GGN-GAY-GAY-


 


GGN-GGN, GGN-GGN-GGN-GAY-GGN-GAY-GGN, GGN-GGN-GGN-


 


GAY-GGN-GGN-GAY, GGN-GGN-GGN-GGN-GAY-GAY-GGN, GGN-


 


GGN-GGN-GGN-GAY-GGN-GAY-GGN-GGN-GGN-GGN-GGN-GGN-


 


GAY, GAY-GGN-GGN-GGN-GGN-GGN-GGN, GGN-GAY-GGN-GGN-


 


GGN-GGN-GGN, GGN-GGN-GAY-GGN-GGN-GGN-GGN, GGN-GGN-


 


GGN-GAY-GGN-GGN-GGN, GGN-GGN-GGN-GGN-GAY-GGN-GGN, 


 


GGN-GGN-GGN-GGN-GGN-GAY-GGN


 


Q (glutamine) as major constituent


Oligonucleotides of peptide motifs containing 3-7 


amino acide residues with


Q(Glutamine) as the major constituent and 


T(Threonine) as the minor constituent


CAR-CAR-ACN, ACN-CAR-CAR, CAR-ACN-CAR, CAR-CAR-CAR-


 


ACN, ACN-CAR-CAR-CAR, CAR-ACN-CAR-CAR, CAR-CAR-ACN-


 


CAR, CAR-CAR-CAR-CAR-ACN, ACN-CAR-CAR-CAR-CAR, CAR-


 


ACN-CAR-CAR-CAR, CAR-CAR-ACN-CAR-CAR, CAR-CAR-CAR-


 


ACN-CAR, CAR-CAR-CAR-ACN-ACN, ACN-ACN-CAR-CAR-CAR, 


 


ACN-CAR-ACN-CAR-CAR, ACN-CAR-CAR-ACN-CAR, ACN-CAR-


 


CAR-CAR-ACN, CAR-ACN-ACN-CAR-CAR, CAR-ACN-CAR-ACN-


 


CAR, CAR-ACN-CAR-CAR-ACN, CAR-CAR-ACN-ACN-CAR, CAR-


 


CAR-ACN-CAR-ACN, CAR-CAR-CAR-CAR-CAR-ACN, ACN-CAR-


 


CAR-CAR-CAR-CAR, CAR-ACN-CAR-CAR-CAR-CAR, CAR-CAR-


 


ACN-CAR-CAR-CAR, CAR-CAR-CAR-ACN-CAR-CAR, CAR-CAR-


 


CAR-CAR-ACN-CAR, CAR-CAR-CAR-CAR-ACN-ACN, ACN-ACN-


 


CAR-CAR-CAR-CAR, ACN-CAR-ACN-CAR-CAR-CAR, ACN-CAR-


 


CAR-ACN-CAR-CAR, ACN-CAR-CAR-CAR-ACN-CAR, ACN-CAR-


 


CAR-CAR-CAR-ACN, CAR-ACN-ACN-CAR-CAR-CAR, CAR-ACN-


 


CAR-ACN-CAR-CAR, CAR-ACN-CAR-CAR-ACN-CAR, CAR-ACN-


 


CAR-CAR-CAR-ACN, CAR-CAR-ACN-ACN-CAR-CAR, CAR-CAR-


 


ACN-CAR-ACN-CAR, CAR-CAR-ACN-CAR-CAR-ACN, CAR-CAR-


 


CAR-ACN-ACN-CAR, CAR-CAR-CAR-ACN-CAR-ACN, CAR-CAR-


 


CAR-CAR-ACN-ACN-ACN, ACN-ACN-ACN-CAR-CAR-CAR-CAR, 


 


ACN-CAR-ACN-ACN-CAR-CAR-CAR, ACN-CAR-ACN-CAR-ACN-


 


CAR-CAR, ACN-CAR-ACN-CAR-CAR-ACN-CAR, ACN-CAR-ACN-


 


CAR-CAR-CAR-ACN, ACN-CAR-CAR-ACN-ACN-CAR-CAR, ACN-


 


CAR-CAR-ACN-CAR-ACN-CAR, ACN-CAR-CAR-ACN-CAR-CAR-


 


ACN, ACN-CAR-CAR-CAR-ACN-CAR-ACN, ACN-CAR-CAR-CAR-


 


ACN-ACN-CAR, ACN-CAR-CAR-CAR-CAR-ACN-ACN, ACN-ACN-


 


CAR-ACN-CAR-CAR-CAR, ACN-ACN-CAR-CAR-ACN-CAR-CAR, 


 


ACN-ACN-CAR-CAR-CAR-ACN-CAR, ACN-ACN-CAR-CAR-CAR-


 


CAR-ACN, CAR-ACN-ACN-ACN-CAR-CAR-CAR, CAR-ACN-ACN-


 


CAR-ACN-CAR-CAR, CAR-ACN-ACN-CAR-CAR-ACN-CAR, CAR-


 


ACN-ACN-CAR-CAR-CAR-ACN, CAR-ACN-CAR-ACN-ACN-CAR-


 


CAR, CAR-ACN-CAR-CAR-ACN-ACN-CAR, CAR-ACN-CAR-CAR-


 


CAR-ACN-ACN, CAR-ACN-CAR-ACN-CAR-ACN-CAR, CAR-ACN-


 


CAR-ACN-CAR-CAR-ACN, CAR-ACN-CAR-CAR-ACN-CAR-ACN, 


 


CAR-CAR-ACN-ACN-ACN-CAR-CAR, CAR-CAR-ACN-ACN-CAR-


 


ACN-CAR, CAR-CAR-ACN-ACN-CAR-CAR-ACN, CAR-CAR-ACN-


 


CAR-ACN-ACN-CAR, CAR-CAR-ACN-CAR-ACN-CAR-ACN, CAR-


 


CAR-ACN-CAR-CAR-ACN-ACN, CAR-CAR-CAR-ACN-ACN-ACN-


 


CAR, CAR-CAR-CAR-ACN-ACN-CAR-ACN, CAR-CAR-CAR-ACN-


 


CAR-ACN-ACN, CAR-CAR-CAR-CAR-CAR-ACN-ACN, ACN-ACN-


 


CAR-CAR-CAR-CAR-CAR, ACN-CAR-ACN-CAR-CAR-CAR-CAR, 


 


ACN-CAR-CAR-ACN-CAR-CAR-CAR, ACN-CAR-CAR-CAR-ACN-


 


CAR-CAR, ACN-CAR-CAR-CAR-CAR-ACN-CAR, ACN-CAR-CAR-


 


CAR-CAR-CAR-ACN, CAR-ACN-ACN-CAR-CAR-CAR-CAR, CAR-


 


ACN-CAR-ACN-CAR-CAR-CAR, CAR-ACN-CAR-CAR-ACN-CAR-


 


CAR, CAR-ACN-CAR-CAR-CAR-ACN-CAR, CAR-ACN-CAR-CAR-


 


CAR-CAR-ACN, CAR-CAR-ACN-ACN-CAR-CAR-CAR, CAR-CAR-


 


ACN-CAR-ACN-CAR-CAR, CAR-CAR-ACN-CAR-CAR-ACN-CAR,


 


CAR-CAR-ACN-CAR-CAR-CAR-ACN, CAR-CAR-CAR-ACN-ACN-


 


CAR-CAR, CAR-CAR-CAR-ACN-CAR-ACN-CAR, CAR-CAR-CAR-


 


ACN-CAR-CAR-ACN, CAR-CAR-CAR-CAR-ACN-ACN-CAR, CAR-


 


CAR-CAR-CAR-ACN-CAR-ACN-CAR-CAR-CAR-CAR-CAR-CAR-ACN, 


 


ACN-CAR-CAR-CAR-CAR-CAR-CAR, CAR-ACN-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-ACN-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


ACN-CAR-CAR-CAR, CAR-CAR-CAR-CAR-ACN-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-ACN-CAR


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


Q(Glutamine) as the major constituent and 


A(Alanine) as the minor constituent


CAR-CAR-GCN, GCN-CAR-CAR, CAR-GCN-CAR, CAR-CAR-CAR-


 


GCN, GCN-CAR-CAR-CAR, CAR-GCN-CAR-CAR, CAR-CAR-GCN-


 


CAR, CAR-CAR-CAR-CAR-GCN, GCN-CAR-CAR-CAR-CAR, CAR-


 


GCN-CAR-CAR-CAR, CAR-CAR-GCN-CAR-CAR, CAR-CAR-CAR-


 


GCN-CAR, CAR-CAR-CAR-GCN-GCN, GCN-GCN-CAR-CAR-CAR, 


 


GCN-CAR-GCN-CAR-CAR, GCN-CAR-CAR-GCN-CAR, GCN-CAR-


 


CAR-CAR-GCN, CAR-GCN-GCN-CAR-CAR, CAR-GCN-CAR-GCN-


 


CAR, CAR-GCN-CAR-CAR-GCN, CAR-CAR-GCN-GCN-CAR, CAR-


 


CAR-GCN-CAR-GCN, CAR-CAR-CAR-CAR-CAR-GCN, GCN-CAR-


 


CAR-CAR-CAR-CAR, CAR-GCN-CAR-CAR-CAR-CAR, CAR-CAR-


 


GCN-CAR-CAR-CAR, CAR-CAR-CAR-GCN-CAR-CAR, CAR-CAR-


 


CAR-CAR-GCN-CAR, CAR-CAR-CAR-CAR-GCN-GCN, GCN-GCN-


 


CAR-CAR-CAR-CAR, GCN-CAR-GCN-CAR-CAR-CAR, GCN-CAR-


 


CAR-GCN-CAR-CAR, GCN-CAR-CAR-CAR-GCN-CAR, GCN-CAR-


 


CAR-CAR-CAR-GCN, CAR-GCN-GCN-CAR-CAR-CAR, CAR-GCN-


 


CAR-GCN-CAR-CAR, CAR-GCN-CAR-CAR-GCN-CAR, CAR-GCN-


 


CAR-CAR-CAR-GCN, CAR-CAR-GCN-GCN-CAR-CAR, CAR-CAR-


 


GCN-CAR-GCN-CAR, CAR-CAR-GCN-CAR-CAR-GCN, CAR-CAR-


 


CAR-GCN-GCN-CAR, CAR-CAR-CAR-GCN-CAR-GCN, CAR-CAR-


 


CAR-CAR-GCN-GCN-GCN, GCN-GCN-GCN-CAR-CAR-CAR-CAR, 


 


GCN-CAR-GCN-GCN-CAR-CAR-CAR, GCN-CAR-GCN-CAR-GCN-


 


CAR-CAR, GCN-CAR-GCN-CAR-CAR-GCN-CAR, GCN-CAR-GCN-


 


CAR-CAR-CAR-GCN, GCN-CAR-CAR-GCN-GCN-CAR-CAR, GCN-


 


CAR-CAR-GCN-CAR-GCN-CAR, GCN-CAR-CAR-GCN-CAR-CAR-


 


GCN, GCN-CAR-CAR-CAR-GCN-CAR-GCN, GCN-CAR-CAR-CAR-


 


GCN-GCN-CAR, GCN-CAR-CAR-CAR-CAR-GCN-GCN, GCN-GCN-


 


CAR-GCN-CAR-CAR-CAR, GCN-GCN-CAR-CAR-GCN-CAR-CAR, 


 


GCN-GCN-CAR-CAR-CAR-GCN-CAR, GCN-GCN-CAR-CAR-CAR-


 


CAR-GCN, CAR-GCN-GCN-GCN-CAR-CAR-CAR, CAR-GCN-GCN-


 


CAR-GCN-CAR-CAR, CAR-GCN-GCN-CAR-CAR-GCN-CAR, CAR-


 


GCN-GCN-CAR-CAR-CAR-GCN, CAR-GCN-CAR-GCN-GCN-CAR-


 


CAR, CAR-GCN-CAR-CAR-GCN-GCN-CAR, CAR-GCN-CAR-CAR-


 


CAR-GCN-GCN, CAR-GCN-CAR-GCN-CAR-GCN-CAR, CAR-GCN-


 


CAR-GCN-CAR-CAR-GCN, CAR-GCN-CAR-CAR-GCN-CAR-GCN, 


 


CAR-CAR-GCN-GCN-GCN-CAR-CAR, CAR-CAR-GCN-GCN-CAR-


 


GCN-CAR, CAR-CAR-GCN-GCN-CAR-CAR-GCN, CAR-CAR-GCN-


 


CAR-GCN-GCN-CAR, CAR-CAR-GCN-CAR-GCN-CAR-GCN, CAR-


 


CAR-GCN-CAR-CAR-GCN-GCN, CAR-CAR-CAR-GCN-GCN-GCN-


 


CAR, CAR-CAR-CAR-GCN-GCN-CAR-GCN, CAR-CAR-CAR-GCN-


 


GCAR-GCN-GCN, CAR-CAR-CAR-CAR-CAR-CN-GCN, GCN-GCN-


 


CAR-CAR-CAR-CAR-CAR, GCN-CAR-GCN-CAR-CAR-CAR-CAR, 


 


GCN-CAR-CAR-GCN-CAR-CAR-CAR, GCN-CAR-CAR-CAR-GCN-


 


CAR-CAR, GCN-CAR-CAR-CAR-CAR-GCN-CAR, GCN-CAR-CAR-


 


CAR-CAR-CAR-GCN, CAR-GCN-GCN-CAR-CAR-CAR-CAR, CAR-


 


GCN-CAR-GCN-CAR-CAR-CAR, CAR-GCN-CAR-CAR-GCN-CAR-


 


CAR, CAR-GCN-CAR-CAR-CAR-GCN-CAR, CAR-GCN-CAR-CAR-


 


CAR-CAR-GCN, CAR-CAR-GCN-GCN-CAR-CAR-CAR, CAR-CAR-


 


GCN-CAR-GCN-CAR-CAR, CAR-CAR-GCN-CAR-CAR-GCN-CAR, 


 


CAR-CAR-GCN-CAR-CAR-CAR-GCN, CAR-CAR-CAR-GCN-GCN-


 


CAR-CAR, CAR-CAR-CAR-GCN-CAR-GCN-CAR, CAR-CAR-CAR-


 


GCN-CAR-CAR-GCN, CAR-CAR-CAR-CAR-GCN-GCN-CAR, CAR-


 


CAR-CAR-CAR-GCN-CAR-GCN-CAR-CAR-CAR-CAR-CAR-CAR-GCN, 


 


GCN-CAR-CAR-CAR-CAR-CAR-CAR, CAR-GCN-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-GCN-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


GCN-CAR-CAR-CAR, CAR-CAR-CAR-CAR-GCN-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-GCN-CAR


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


Q(Glutamine) as the major constituent 


and S(Serine) as the minor constituent


CAR-CAR-AGY, AGY-CAR-CAR, CAR-AGY-CAR, CAR-CAR-CAR-


 


AGY, AGY-CAR-CAR-CAR, CAR-AGY-CAR-CAR, CAR-CAR-AGY-


 


CAR, CAR-CAR-CAR-CAR-AGY, AGY-CAR-CAR-CAR-CAR, CAR-


 


AGY-CAR-CAR-CAR, CAR-CAR-AGY-CAR-CAR, CAR-CAR-CAR-


 


AGY-CAR, CAR-CAR-CAR-AGY-AGY, AGY-AGY-CAR-CAR-CAR, 


 


AGY-CAR-AGY-CAR-CAR, AGY-CAR-CAR-AGY-CAR, AGY-CAR-


 


CAR-CAR-AGY, CAR-AGY-AGY-CAR-CAR, CAR-AGY-CAR-AGY-


 


CAR, CAR-AGY-CAR-CAR-AGY, CAR-CAR-AGY-AGY-CAR, CAR-


 


CAR-AGY-CAR-AGY, CAR-CAR-CAR-CAR-CAR-AGY, AGY-CAR-


 


CAR-CAR-CAR-CAR, CAR-AGY-CAR-CAR-CAR-CAR, CAR-CAR-


 


AGY-CAR-CAR-CAR, CAR-CAR-CAR-AGY-CAR-CAR, CAR-CAR-


 


CAR-CAR-AGY-CAR, CAR-CAR-CAR-CAR-AGY-AGY, AGY-AGY-


 


CAR-CAR-CAR-CAR, AGY-CAR-AGY-CAR-CAR-CAR, AGY-CAR-


 


CAR-AGY-CAR-CAR, AGY-CAR-CAR-CAR-AGY-CAR, AGY-CAR-


 


CAR-CAR-CAR-AGY, CAR-AGY-AGY-CAR-CAR-CAR, CAR-AGY-


 


CAR-AGY-CAR-CAR, CAR-AGY-CAR-CAR-AGY-CAR, CAR-AGY-


 


CAR-CAR-CAR-AGY, CAR-CAR-AGY-AGY-CAR-CAR, CAR-CAR-


 


AGY-CAR-AGY-CAR, CAR-CAR-AGY-CAR-CAR-AGY, CAR-CAR-


 


CAR-AGY-AGY-CAR, CAR-CAR-CAR-AGY-CAR-AGY, CAR-CAR-


 


CAR-CAR-AGY-AGY-AGY, AGY-AGY-AGY-CAR-CAR-CAR-CAR, 


 


AGY-CAR-AGY-AGY-CAR-CAR-CAR, AGY-CAR-AGY-CAR-AGY-CAR-CAR, AGY-CAR-AGY-CAR-CAR-AGY-CAR, AGY-CAR-AGY-


 


CAR-CAR-CAR-AGY, AGY-CAR-CAR-AGY-AGY-CAR-CAR, AGY-


 


CAR-CAR-AGY-CAR-AGY-CAR, AGY-CAR-CAR-AGY-CAR-CAR-


 


AGY, AGY-CAR-CAR-CAR-AGY-CAR-AGY, AGY-CAR-CAR-CAR-


 


AGY-AGY-CAR, AGY-CAR-CAR-CAR-CAR-AGY-AGY, AGY-AGY-


 


CAR-AGY-CAR-CAR-CAR, AGY-AGY-CAR-CAR-AGY-CAR-CAR, 


 


AGY-AGY-CAR-CAR-CAR-AGY-CAR, AGY-AGY-CAR-CAR-CAR-


 


CAR-AGY, CAR-AGY-AGY-AGY-CAR-CAR-CAR, CAR-AGY-AGY-


 


CAR-AGY-CAR-CAR, CAR-AGY-AGY-CAR-CAR-AGY-CAR, CAR-


 


AGY-AGY-CAR-CAR-CAR-AGY, CAR-AGY-CAR-AGY-AGY-CAR-


 


CAR, CAR-AGY-CAR-CAR-AGY-AGY-CAR, CAR-AGY-CAR-CAR-


 


CAR-AGY-AGY, CAR-AGY-CAR-AGY-CAR-AGY-CAR, CAR-AGY-


 


CAR-AGY-CAR-CAR-AGY, CAR-AGY-CAR-CAR-AGY-CAR-AGY, 


 


CAR-CAR-AGY-AGY-AGY-CAR-CAR, CAR-CAR-AGY-AGY-CAR-


 


AGY-CAR, CAR-CAR-AGY-AGY-CAR-CAR-AGY, CAR-CAR-AGY-


 


CAR-AGY-AGY-CAR, CAR-CAR-AGY-CAR-AGY-CAR-AGY, CAR-


 


CAR-AGY-CAR-CAR-AGY-AGY, CAR-CAR-CAR-AGY-AGY-AGY-


 


CAR, CAR-CAR-CAR-AGY-AGY-CAR-AGY, CAR-CAR-CAR-AGY-


 


CAR-AGY-AGY, CAR-CAR-CAR-CAR-CAR-AGY-AGY, AGY-AGY-


 


CAR-CAR-CAR-CAR-CAR, AGY-CAR-AGY-CAR-CAR-CAR-CAR, 


 


AGY-CAR-CAR-AGY-CAR-CAR-CAR, AGY-CAR-CAR-CAR-AGY-


 


CAR-CAR, AGY-CAR-CAR-CAR-CAR-AGY-CAR, AGY-CAR-CAR-


 


CAR-CAR-CAR-AGY, CAR-AGY-AGY-CAR-CAR-CAR-CAR, CAR-


 


AGY-CAR-AGY-CAR-CAR-CAR, CAR-AGY-CAR-CAR-AGY-CAR-


 


CAR, CAR-AGY-CAR-CAR-CAR-AGY-CAR, CAR-AGY-CAR-CAR-


 


CAR-CAR-AGY, CAR-CAR-AGY-AGY-CAR-CAR-CAR, CAR-CAR-


 


AGY-CAR-AGY-CAR-CAR, CAR-CAR-AGY-CAR-CAR-AGY-CAR, 


 


CAR-CAR-AGY-CAR-CAR-CAR-AGY, CAR-CAR-CAR-AGY-AGY-


 


CAR-CAR, CAR-CAR-CAR-AGY-CAR-AGY-CAR, CAR-CAR-CAR-


 


AGY-CAR-CAR-AGY, CAR-CAR-CAR-CAR-AGY-AGY-CAR, CAR-


 


CAR-CAR-CAR-AGY-CAR-AGY-CAR-CAR-CAR-CAR-CAR-CAR-AGY, 


 


AGY-CAR-CAR-CAR-CAR-CAR-CAR, CAR-AGY-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-AGY-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


AGY-CAR-CAR-CAR, CAR-CAR-CAR-CAR-AGY-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-AGY-CAR


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


Q(Glutamine) as the major constituent


and E(Glutamic Acid) as the minor constituent


CAR-CAR-GAR, GAR-CAR-CAR, CAR-GAR-CAR, CAR-CAR-CAR-


 


GAR, GAR-CAR-CAR-CAR, CAR-GAR-CAR-CAR, CAR-CAR-GAR-


 


CAR, CAR-CAR-CAR-CAR-GAR, GAR-CAR-CAR-CAR-CAR, CAR-


 


GAR-CAR-CAR-CAR, CAR-CAR-GAR-CAR-CAR, CAR-CAR-CAR-


 


GAR-CAR, CAR-CAR-CAR-GAR-GAR, GAR-GAR-CAR-CAR-CAR, 


 


GAR-CAR-GAR-CAR-CAR, GAR-CAR-CAR-GAR-CAR, GAR-CAR-


 


CAR-CAR-GAR, CAR-GAR-GAR-CAR-CAR, CAR-GAR-CAR-GAR-


 


CAR, CAR-GAR-CAR-CAR-GAR, CAR-CAR-GAR-GAR-CAR, CAR-


 


CAR-GAR-CAR-GAR, CAR-CAR-CAR-CAR-CAR-GAR, GAR-CAR-


 


CAR-CAR-CAR-CAR, CAR-GAR-CAR-CAR-CAR-CAR, CAR-CAR-


 


GAR-CAR-CAR-CAR, CAR-CAR-CAR-GAR-CAR-CAR, CAR-CAR-


 


CAR-CAR-GAR-CAR, CAR-CAR-CAR-CAR-GAR-GAR, GAR-GAR-


 


CAR-CAR-CAR-CAR, GAR-CAR-GAR-CAR-CAR-CAR, GAR-CAR-


 


CAR-GAR-CAR-CAR, GAR-CAR-CAR-CAR-GAR-CAR, GAR-CAR-


 


CAR-CAR-CAR-GAR, CAR-GAR-GAR-CAR-CAR-CAR, CAR-GAR-


 


CAR-GAR-CAR-CAR, CAR-GAR-CAR-CAR-GAR-CAR, CAR-GAR-


 


CAR-CAR-CAR-GAR, CAR-CAR-GAR-GAR-CAR-CAR, CAR-CAR-


 


GAR-CAR-GAR-CAR, CAR-CAR-GAR-CAR-CAR-GAR, CAR-CAR-


 


CAR-GAR-GAR-CAR, CAR-CAR-CAR-GAR-CAR-GAR, CAR-CAR-


 


CAR-CAR-GAR-GAR-GAR, GAR-GAR-GAR-CAR-CAR-CAR-CAR, 


 


GAR-CAR-GAR-GAR-CAR-CAR-CAR, GAR-CAR-GAR-CAR-GAR-


 


CAR-CAR, GAR-CAR-GAR-CAR-CAR-GAR-CAR, GAR-CAR-GAR-


 


CAR-CAR-CAR-GAR, GAR-CAR-CAR-GAR-GAR-CAR-CAR, GAR-


 


CAR-CAR-GAR-CAR-GAR-CAR, GAR-CAR-CAR-GAR-CAR-CAR-


 


GAR, GAR-CAR-CAR-CAR-GAR-CAR-GAR, GAR-CAR-CAR-CAR-


 


GAR-GAR-CAR, GAR-CAR-CAR-CAR-CAR-GAR-GAR, GAR-GAR-


 


CAR-GAR-CAR-CAR-CAR, GAR-GAR-CAR-CAR-GAR-CAR-CAR, 


 


GAR-GAR-CAR-CAR-CAR-GAR-CAR, GAR-GAR-CAR-CAR-CAR-


 


CAR-GAR, CAR-GAR-GAR-GAR-CAR-CAR-CAR, CAR-GAR-GAR-


 


CAR-GAR-CAR-CAR, CAR-GAR-GAR-CAR-CAR-GAR-CAR, CAR-


 


GAR-GAR-CAR-CAR-CAR-GAR, CAR-GAR-CAR-GAR-GAR-CAR-


 


CAR, CAR-GAR-CAR-CAR-GAR-GAR-CAR, CAR-GAR-CAR-CAR-


 


CAR-GAR-GAR, CAR-GAR-CAR-GAR-CAR-GAR-CAR, CAR-GAR-


 


CAR-GAR-CAR-CAR-GAR, CAR-GAR-CAR-CAR-GAR-CAR-GAR, 


 


CAR-CAR-GAR-GAR-GAR-CAR-CAR, CAR-CAR-GAR-GAR-CAR-


 


GAR-CAR, CAR-CAR-GAR-GAR-CAR-CAR-GAR, CAR-CAR-GAR-


 


CAR-GAR-GAR-CAR, CAR-CAR-GAR-CAR-GAR-CAR-GAR, CAR-


 


CAR-GAR-CAR-CAR-GAR-GAR, CAR-CAR-CAR-GAR-GAR-GAR-


 


CAR, CAR-CAR-CAR-GAR-GAR-CAR-GAR, CAR-CAR-CAR-GAR-


 


CAR-GAR-GAR, CAR-CAR-CAR-CAR-CAR-GAR-GAR, GAR-GAR-


 


CAR-CAR-CAR-CAR-CAR, GAR-CAR-GAR-CAR-CAR-CAR-CAR, 


 


GAR-CAR-CAR-GAR-CAR-CAR-CAR, GAR-CAR-CAR-CAR-GAR-


 


CAR-CAR, GAR-CAR-CAR-CAR-CAR-GAR-CAR, GAR-CAR-CAR-


 


CAR-CAR-CAR-GAR, CAR-GAR-GAR-CAR-CAR-CAR-CAR, CAR-


 


GAR-CAR-GAR-CAR-CAR-CAR, CAR-GAR-CAR-CAR-GAR-CAR-


 


CAR, CAR-GAR-CAR-CAR-CAR-GAR-CAR, CAR-GAR-CAR-CAR-


 


CAR-CAR-GAR, CAR-CAR-GAR-GAR-CAR-CAR-CAR, CAR-CAR-


 


GAR-CAR-GAR-CAR-CAR, CAR-CAR-GAR-CAR-CAR-GAR-CAR, 


 


CAR-CAR-GAR-CAR-CAR-CAR-GAR, CAR-CAR-CAR-GAR-GAR-


 


CAR-CAR, CAR-CAR-CAR-GAR-CAR-GAR-CAR, CAR-CAR-CAR-


 


GAR-CAR-CAR-GAR, CAR-CAR-CAR-CAR-GAR-GAR-CAR, CAR-


 


CAR-CAR-CAR-GAR-CAR-GAR-CAR-CAR-CAR-CAR-CAR-CAR-GAR, 


 


GAR-CAR-CAR-CAR-CAR-CAR-CAR, CAR-GAR-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-GAR-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


GAR-CAR-CAR-CAR, CAR-CAR-CAR-CAR-GAR-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-GAR-CAR


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


Q(Glutamine) as the major constituent 


and H(Histidine) as the minor constituent


CAR-CAR-CAY, CAY-CAR-CAR, CAR-CAY-CAR, CAR-CAR-CAR-


 


CAY, CAY-CAR-CAR-CAR, CAR-CAY-CAR-CAR, CAR-CAR-CAY-


 


CAR, CAR-CAR-CAR-CAR-CAY, CAY-CAR-CAR-CAR-CAR, CAR-


 


CAY-CAR-CAR-CAR, CAR-CAR-CAY-CAR-CAR, CAR-CAR-CAR-


 


CAY-CAR, CAR-CAR-CAR-CAY-CAY, CAY-CAY-CAR-CAR-CAR, 


 


CAY-CAR-CAY-CAR-CAR, CAY-CAR-CAR-CAY-CAR, CAY-CAR-


 


CAR-CAR-CAY, CAR-CAY-CAY-CAR-CAR, CAR-CAY-CAR-CAY-


 


CAR, CAR-CAY-CAR-CAR-CAY, CAR-CAR-CAY-CAY-CAR, CAR-


 


CAR-CAY-CAR-CAY, CAR-CAR-CAR-CAR-CAR-CAY, CAY-CAR-


 


CAR-CAR-CAR-CAR, CAR-CAY-CAR-CAR-CAR-CAR, CAR-CAR-


 


CAY-CAR-CAR-CAR, CAR-CAR-CAR-CAY-CAR-CAR, CAR-CAR-


 


CAR-CAR-CAY-CAR, CAR-CAR-CAR-CAR-CAY-CAY, CAY-CAY-


 


CAR-CAR-CAR-CAR, CAY-CAR-CAY-CAR-CAR-CAR, CAY-CAR-


 


CAR-CAY-CAR-CAR, CAY-CAR-CAR-CAR-CAY-CAR, CAY-CAR-


 


CAR-CAR-CAR-CAY, CAR-CAY-CAY-CAR-CAR-CAR, CAR-CAY-


 


CAR-CAY-CAR-CAR, CAR-CAY-CAR-CAR-CAY-CAR, CAR-CAY-


 


CAR-CAR-CAR-CAY, CAR-CAR-CAY-CAY-CAR-CAR, CAR-CAR-


 


CAY-CAR-CAY-CAR, CAR-CAR-CAY-CAR-CAR-CAY, CAR-CAR-


 


CAR-CAY-CAY-CAR, CAR-CAR-CAR-CAY-CAR-CAY, CAR-CAR-


 


CAR-CAR-CAY-CAY-CAY, CAY-CAY-CAY-CAR-CAR-CAR-CAR, 


 


CAY-CAR-CAY-CAY-CAR-CAR-CAR, CAY-CAR-CAY-CAR-CAY-


 


CAR-CAR, CAY-CAR-CAY-CAR-CAR-CAY-CAR, CAY-CAR-CAY-


 


CAR-CAR-CAR-CAY, CAY-CAR-CAR-CAY-CAY-CAR-CAR, CAY-


 


CAR-CAR-CAY-CAR-CAY-CAR, CAY-CAR-CAR-CAY-CAR-CAR-


 


CAY, CAY-CAR-CAR-CAR-CAY-CAR-CAY, CAY-CAR-CAR-CAR-


 


CAY-CAY-CAR, CAY-CAR-CAR-CAR-CAR-CAY-CAY, CAY-CAY-


 


CAR-CAY-CAR-CAR-CAR, CAY-CAY-CAR-CAR-CAY-CAR-CAR, 


 


CAY-CAY-CAR-CAR-CAR-CAY-CAR, CAY-CAY-CAR-CAR-CAR-


 


CAR-CAY, CAR-CAY-CAY-CAY-CAR-CAR-CAR, CAR-CAY-CAY-


 


CAR-CAY-CAR-CAR, CAR-CAY-CAY-CAR-CAR-CAY-CAR, CAR-


 


CAY-CAY-CAR-CAR-CAR-CAY, CAR-CAY-CAR-CAY-CAY-CAR-


 


CAR, CAR-CAY-CAR-CAR-CAY-CAY-CAR, CAR-CAY-CAR-CAR-


 


CAR-CAY-CAY, CAR-CAY-CAR-CAY-CAR-CAY-CAR, CAR-CAY-


 


CAR-CAY-CAR-CAR-CAY, CAR-CAY-CAR-CAR-CAY-CAR-CAY, 


 


CAR-CAR-CAY-CAY-CAY-CAR-CAR, CAR-CAR-CAY-CAY-CAR-


 


CAY-CAR, CAR-CAR-CAY-CAY-CAR-CAR-CAY, CAR-CAR-CAY-


 


CAR-CAY-CAY-CAR, CAR-CAR-CAY-CAR-CAY-CAR-CAY, CAR-


 


CAR-CAY-CAR-CAR-CAY-CAY, CAR-CAR-CAR-CAY-CAY-CAY-


 


CAR, CAR-CAR-CAR-CAY-CAY-CAR-CAY, CAR-CAR-CAR-CAY-


 


CAR-CAY-CAY, CAR-CAR-CAR-CAR-CAR-CAY-CAY, CAY-CAY-


 


CAR-CAR-CAR-CAR-CAR, CAY-CAR-CAY-CAR-CAR-CAR-CAR, 


 


CAY-CAR-CAR-CAY-CAR-CAR-CAR, CAY-CAR-CAR-CAR-CAY-


 


CAR-CAR, CAY-CAR-CAR-CAR-CAR-CAY-CAR, CAY-CAR-CAR-


 


CAR-CAR-CAR-CAY, CAR-CAY-CAY-CAR-CAR-CAR-CAR, CAR-


 


CAY-CAR-CAY-CAR-CAR-CAR, CAR-CAY-CAR-CAR-CAY-CAR-


 


CAR, CAR-CAY-CAR-CAR-CAR-CAY-CAR, CAR-CAY-CAR-CAR-


 


CAR-CAR-CAY, CAR-CAR-CAY-CAY-CAR-CAR-CAR, CAR-CAR-


 


CAY-CAR-CAY-CAR-CAR, CAR-CAR-CAY-CAR-CAR-CAY-CAR, 


 


CAR-CAR-CAY-CAR-CAR-CAR-CAY, CAR-CAR-CAR-CAY-CAY-


 


CAR-CAR, CAR-CAR-CAR-CAY-CAR-CAY-CAR, CAR-CAR-CAR-


 


CAY-CAR-CAR-CAY, CAR-CAR-CAR-CAR-CAY-CAY-CAR, CAR-


 


CAR-CAR-CAR-CAY-CAR-CAY-CAR-CAR-CAR-CAR-CAR-CAR-CAY, 


 


CAY-CAR-CAR-CAR-CAR-CAR-CAR, CAR-CAY-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-CAY-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


CAY-CAR-CAR-CAR, CAR-CAR-CAR-CAR-CAY-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-CAY-CAR


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


Q(Glutamine) as the major constituent 


and N(Asparagine) as the minor constituent


CAR-CAR-AAY, AAY-CAR-CAR, CAR-AAY-CAR, CAR-CAR-CAR-


 


AAY, AAY-CAR-CAR-CAR, CAR-AAY-CAR-CAR, CAR-CAR-AAY-


 


CAR, CAR-CAR-CAR-CAR-AAY, AAY-CAR-CAR-CAR-CAR, CAR-


 


AAY-CAR-CAR-CAR, CAR-CAR-AAY-CAR-CAR, CAR-CAR-CAR-


 


AAY-CAR, CAR-CAR-CAR-AAY-AAY, AAY-AAY-CAR-CAR-CAR, 


 


AAY-CAR-AAY-CAR-CAR, AAY-CAR-CAR-AAY-CAR, AAY-CAR-


 


CAR-CAR-AAY, CAR-AAY-AAY-CAR-CAR, CAR-AAY-CAR-AAY-


 


CAR, CAR-AAY-CAR-CAR-AAY, CAR-CAR-AAY-AAY-CAR, CAR-


 


CAR-AAY-CAR-AAY, CAR-CAR-CAR-CAR-CAR-AAY, AAY-CAR-


 


CAR-CAR-CAR-CAR, CAR-AAY-CAR-CAR-CAR-CAR, CAR-CAR-


 


AAY-CAR-CAR-CAR, CAR-CAR-CAR-AAY-CAR-CAR, CAR-CAR-


 


CAR-CAR-AAY-CAR, CAR-CAR-CAR-CAR-AAY-AAY, AAY-AAY-


 


CAR-CAR-CAR-CAR, AAY-CAR-AAY-CAR-CAR-CAR, AAY-CAR-


 


CAR-AAY-CAR-CAR, AAY-CAR-CAR-CAR-AAY-CAR, AAY-CAR-


 


CAR-CAR-CAR-AAY, CAR-AAY-AAY-CAR-CAR-CAR, CAR-AAY-


 


CAR-AAY-CAR-CAR, CAR-AAY-CAR-CAR-AAY-CAR, CAR-AAY-


 


CAR-CAR-CAR-AAY, CAR-CAR-AAY-AAY-CAR-CAR, CAR-CAR-


 


AAY-CAR-AAY-CAR, CAR-CAR-AAY-CAR-CAR-AAY, CAR-CAR-


 


CAR-AAY-AAY-CAR, CAR-CAR-CAR-AAY-CAR-AAY, CAR-CAR-


 


CAR-CAR-AAY-AAY-AAY, AAY-AAY-AAY-CAR-CAR-CAR-CAR, 


 


AAY-CAR-AAY-AAY-CAR-CAR-CAR, AAY-CAR-AAY-CAR-AAY-


 


CAR-CAR, AAY-CAR-AAY-CAR-CAR-AAY-CAR, AAY-CAR-AAY-


 


CAR-CAR-CAR-AAY, AAY-CAR-CAR-AAY-AAY-CAR-CAR, AAY-


 


CAR-CAR-AAY-CAR-AAY-CAR, AAY-CAR-CAR-AAY-CAR-CAR-


 


AAY, AAY-CAR-CAR-CAR-AAY-CAR-AAY, AAY-CAR-CAR-CAR-


 


AAY-AAY-CAR, AAY-CAR-CAR-CAR-CAR-AAY-AAY, AAY-AAY-


 


CAR-AAY-CAR-CAR-CAR, AAY-AAY-CAR-CAR-AAY-CAR-CAR, 


 


AAY-AAY-CAR-CAR-CAR-AAY-CAR, AAY-AAY-CAR-CAR-CAR-


 


CAR-AAY, CAR-AAY-AAY-AAY-CAR-CAR-CAR, CAR-AAY-AAY-


 


CAR-AAY-CAR-CAR, CAR-AAY-AAY-CAR-CAR-AAY-CAR, CAR-


 


AAY-AAY-CAR-CAR-CAR-AAY, CAR-AAY-CAR-AAY-AAY-CAR-


 


CAR, CAR-AAY-CAR-CAR-AAY-AAY-CAR, CAR-AAY-CAR-CAR-


 


CAR-AAY-AAY, CAR-AAY-CAR-AAY-CAR-AAY-CAR, CAR-AAY-


 


CAR-AAY-CAR-CAR-AAY, CAR-AAY-CAR-CAR-AAY-CAR-AAY, 


 


CAR-CAR-AAY-AAY-AAY-CAR-CAR, CAR-CAR-AAY-AAY-CAR-


 


AAY-CAR, CAR-CAR-AAY-AAY-CAR-CAR-AAY, CAR-CAR-AAY-


 


CAR-AAY-AAY-CAR, CAR-CAR-AAY-CAR-AAY-CAR-AAY, CAR-


 


CAR-AAY-CAR-CAR-AAY-AAY, CAR-CAR-CAR-AAY-AAY-AAY-


 


CAR, CAR-CAR-CAR-AAY-AAY-CAR-AAY, CAR-CAR-CAR-AAY-


 


CAR-AAY-AAY, CAR-CAR-CAR-CAR-CAR-AAY-AAY, AAY-AAY-


 


CAR-CAR-CAR-CAR-CAR, AAY-CAR-AAY-CAR-CAR-CAR-CAR, 


 


AAY-CAR-CAR-AAY-CAR-CAR-CAR, AAY-CAR-CAR-CAR-AAY-


 


CAR-CAR, AAY-CAR-CAR-CAR-CAR-AAY-CAR, AAY-CAR-CAR-


 


CAR-CAR-CAR-AAY, CAR-AAY-AAY-CAR-CAR-CAR-CAR, CAR-


 


AAY-CAR-AAY-CAR-CAR-CAR, CAR-AAY-CAR-CAR-AAY-CAR-


 


CAR, CAR-AAY-CAR-CAR-CAR-AAY-CAR, CAR-AAY-CAR-CAR-


 


CAR-CAR-AAY, CAR-CAR-AAY-AAY-CAR-CAR-CAR, CAR-CAR-


 


AAY-CAR-AAY-CAR-CAR, CAR-CAR-AAY-CAR-CAR-AAY-CAR, 


 


CAR-CAR-AAY-CAR-CAR-CAR-AAY, CAR-CAR-CAR-AAY-AAY-


 


CAR-CAR, CAR-CAR-CAR-AAY-CAR-AAY-CAR, CAR-CAR-CAR-


 


AAY-CAR-CAR-AAY, CAR-CAR-CAR-CAR-AAY-AAY-CAR, CAR-


 


CAR-CAR-CAR-AAY-CAR-AAY-CAR-CAR-CAR-CAR-CAR-CAR-AAY, 


 


AAY-CAR-CAR-CAR-CAR-CAR-CAR, CAR-AAY-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-AAY-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


AAY-CAR-CAR-CAR, CAR-CAR-CAR-CAR-AAY-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-AAY-CAR


 


Oligonucleotides of peptide motifs containing


3-7 amino acide residues with


Q(Glutamine) as the major constituent 


and D(Aspartic Acid) as the minor constituent


CAR-CAR-GAY, GAY-CAR-CAR, CAR-GAY-CAR, CAR-CAR-CAR-


 


GAY, GAY-CAR-CAR-CAR, CAR-GAY-CAR-CAR, CAR-CAR-GAY-


 


CAR, CAR-CAR-CAR-CAR-GAY, GAY-CAR-CAR-CAR-CAR, CAR-


 


GAY-CAR-CAR-CAR, CAR-CAR-GAY-CAR-CAR, CAR-CAR-CAR-


 


GAY-CAR, CAR-CAR-CAR-GAY-GAY, GAY-GAY-CAR-CAR-CAR, 


 


GAY-CAR-GAY-CAR-CAR, GAY-CAR-CAR-GAY-CAR, GAY-CAR-


 


CAR-CAR-GAY, CAR-GAY-GAY-CAR-CAR, CAR-GAY-CAR-GAY-


 


CAR, CAR-GAY-CAR-CAR-GAY, CAR-CAR-GAY-GAY-CAR, CAR-


 


CAR-GAY-CAR-GAY, CAR-CAR-CAR-CAR-CAR-GAY, GAY-CAR-


 


CAR-CAR-CAR-CAR, CAR-GAY-CAR-CAR-CAR-CAR, CAR-CAR-


 


GAY-CAR-CAR-CAR, CAR-CAR-CAR-GAY-CAR-CAR, CAR-CAR-


 


CAR-CAR-GAY-CAR, CAR-CAR-CAR-CAR-GAY-GAY, GAY-GAY-


 


CAR-CAR-CAR-CAR, GAY-CAR-GAY-CAR-CAR-CAR, GAY-CAR-


 


CAR-GAY-CAR-CAR, GAY-CAR-CAR-CAR-GAY-CAR, GAY-CAR-


 


CAR-CAR-CAR-GAY, CAR-GAY-GAY-CAR-CAR-CAR, CAR-GAY-


 


CAR-GAY-CAR-CAR, CAR-GAY-CAR-CAR-GAY-CAR, CAR-GAY-


 


CAR-CAR-CAR-GAY, CAR-CAR-GAY-GAY-CAR-CAR, CAR-CAR-


 


GAY-CAR-GAY-CAR, CAR-CAR-GAY-CAR-CAR-GAY, CAR-CAR-


 


CAR-GAY-GAY-CAR, CAR-CAR-CAR-GAY-CAR-GAY, CAR-CAR-


 


CAR-CAR-GAY-GAY-GAY, GAY-GAY-GAY-CAR-CAR-CAR-CAR, 


 


GAY-CAR-GAY-GAY-CAR-CAR-CAR, GAY-CAR-GAY-CAR-GAY-


 


CAR-CAR, GAY-CAR-GAY-CAR-CAR-GAY-CAR, GAY-CAR-GAY-


 


CAR-CAR-CAR-GAY, GAY-CAR-CAR-GAY-GAY-CAR-CAR, GAY-


 


CAR-CAR-GAY-CAR-GAY-CAR, GAY-CAR-CAR-GAY-CAR-CAR-


 


GAY, GAY-CAR-CAR-CAR-GAY-CAR-GAY, GAY-CAR-CAR-CAR-


 


GAY-GAY-CAR, GAY-CAR-CAR-CAR-CAR-GAY-GAY, GAY-GAY-


 


CAR-GAY-CAR-CAR-CAR, GAY-GAY-CAR-CAR-GAY-CAR-CAR, 


 


GAY-GAY-CAR-CAR-CAR-GAY-CAR, GAY-GAY-CAR-CAR-CAR-


 


CAR-GAY, CAR-GAY-GAY-GAY-CAR-CAR-CAR, CAR-GAY-GAY-


 


CAR-GAY-CAR-CAR, CAR-GAY-GAY-CAR-CAR-GAY-CAR, CAR-


 


GAY-GAY-CAR-CAR-CAR-GAY, CAR-GAY-CAR-GAY-GAY-CAR-


 


CAR, CAR-GAY-CAR-CAR-GAY-GAY-CAR, CAR-GAY-CAR-CAR-


 


CAR-GAY-GAY, CAR-GAY-CAR-GAY-CAR-GAY-CAR, CAR-GAY-


 


CAR-GAY-CAR-CAR-GAY, CAR-GAY-CAR-CAR-GAY-CAR-GAY, 


 


CAR-CAR-GAY-GAY-GAY-CAR-CAR, CAR-CAR-GAY-GAY-CAR-


 


GAY-CAR, CAR-CAR-GAY-GAY-CAR-CAR-GAY, CAR-CAR-GAY-


 


CAR-GAY-GAY-CAR, CAR-CAR-GAY-CAR-GAY-CAR-GAY, CAR-


 


CAR-GAY-CAR-CAR-GAY-GAY, CAR-CAR-CAR-GAY-GAY-GAY-


 


CAR, CAR-CAR-CAR-GAY-GAY-CAR-GAY, CAR-CAR-CAR-GAY-


 


CAR-GAY-GAY, CAR-CAR-CAR-CAR-CAR-GAY-GAY, GAY-GAY-


 


CAR-CAR-CAR-CAR-CAR, GAY-CAR-GAY-CAR-CAR-CAR-CAR, 


 


GAY-CAR-CAR-GAY-CAR-CAR-CAR, GAY-CAR-CAR-CAR-GAY-


 


CAR-CAR, GAY-CAR-CAR-CAR-CAR-GAY-CAR, GAY-CAR-CAR-


 


CAR-CAR-CAR-GAY, CAR-GAY-GAY-CAR-CAR-CAR-CAR, CAR-


 


GAY-CAR-GAY-CAR-CAR-CAR, CAR-GAY-CAR-CAR-GAY-CAR-


 


CAR, CAR-GAY-CAR-CAR-CAR-GAY-CAR, CAR-GAY-CAR-CAR-


 


CAR-CAR-GAY, CAR-CAR-GAY-GAY-CAR-CAR-CAR, CAR-CAR-


 


GAY-CAR-GAY-CAR-CAR, CAR-CAR-GAY-CAR-CAR-GAY-CAR, 


 


CAR-CAR-GAY-CAR-CAR-CAR-GAY, CAR-CAR-CAR-GAY-GAY-


 


CAR-CAR, CAR-CAR-CAR-GAY-CAR-GAY-CAR, CAR-CAR-CAR-


 


GAY-CAR-CAR-GAY, CAR-CAR-CAR-CAR-GAY-GAY-CAR, CAR-


 


CAR-CAR-CAR-GAY-CAR-GAY-CAR-CAR-CAR-CAR-CAR-CAR-GAY, 


 


GAY-CAR-CAR-CAR-CAR-CAR-CAR, CAR-GAY-CAR-CAR-CAR-


 


CAR-CAR, CAR-CAR-GAY-CAR-CAR-CAR-CAR, CAR-CAR-CAR-


 


GAY-CAR-CAR-CAR, CAR-CAR-CAR-CAR-GAY-CAR-CAR, CAR-


 


CAR-CAR-CAR-CAR-GAY-CAR




















TABLE 8









Origin of



Symbol

designation









a
a
adenine



g
g
guanine



c
c
cytosine



t
t
thymine



u
u
uracil



r
g or a
purine



y
t/u or c
pyrimidine



m
a or c
amino



k
g or t/u
keto



s
g or c
strong interactions





3H-bonds



w
a or t/u
weak interactions





2H-bonds



b
g or c or t/u
not a



d
a or g or t/u
not c



h
a or c or t/u
not g



v
a or g or c
not t, not u



n
a or g or c or t/u,
any




unknown, or other

















TABLE 9







(NNT155 disclosed as SEQ ID NO: 2)

























Dose











normalized



Admin
AUC∞
T
AUC/D




AUC∞§


Code
Dose°
ng*
last
h*kg*ng/
t1/2
Cl
Vss
MRT∞
ng*


Construct
μg/kg
h/mL
h
mL/μg
h
mL/h/kg
mL/kg
h
h/mL



















NNT155
2.6
274.5
24
105.6
6.2
9.5
78.2
8.2
316.7


C-GSF
3.2
20.91
8
6.53
1.53
153.0
160.1
1.0
19.60


Control (A)











NEUPOGEN ®30
3.0
47.01
8
15.7
1.13
63.8
77.0
1.2
47.01


NEULASTA
6.0
116.4
24
19.4
3.04
51.5
266.1
5.2
58.20

## Claims

1. A biologically active protein conjugate comprising a biologically active polypeptide coupled via a peptide bond to an amino acid extension comprising from 2 to 75 repeating units of a peptide motif, wherein said peptide motif consists of two residues Asn (N) and one residue of an amino acid selected from the group consisting of Ser (S) and Thr (T), wherein the biologically active polypeptide is human growth hormone SEQ ID NO:2472, granulocyte macrophage colony stimulating factor (GM-CSF; SEQ ID NO:2462), granulocyte colony stimulating factor (G-CSF), macrophage colony stimulating factor (M-CSF; SEQ ID NOs:2454, 2456, 2458, or 2460), colony stimulating factor (CSF), platelet derived growth factor (PDGF), tumor necrosis factor (TNF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor, (FGF), nerve growth factor (NGF), erythropoietin (EPO; SEQ ID NOs:2452, 2480, or 2481), interferon, interferon gamma inducing factor I (IGIF), transforming growth factor beta (TGF-β), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), macrophage inflammatory protein-1-alpha (MIP-1-α), macrophage inflammatory protein-1-β (MIP-1-β), Leishmania elongation initiating factor (LEIF), brain derived neurotrophic factor (BDNF), neurotrophin-2 (NT-2), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), neurotrophin-5 (NT-5), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), a soluble tumor necrosis factor (TNF) type II receptor, a soluble tumor necrosis factor (TNF) type I receptor, a soluble IL-1 receptor type II, a soluble IL-4 receptor, a soluble gp120 glycoprotein, a soluble gp160 glycoprotein, an IL-1 receptor antagonist, a coagulation factor, insulin, activated protein C, Factor VII, collagenase, agalsidase-beta, dornase-alpha, alteplase, pegylated-asparaginase, asparaginase, or imiglucerase, and wherein said biologically active protein conjugate has an increased plasma half-life compared to the plasma half-life of the unmodified biologically active polypeptide.

2. The biologically active protein conjugate of claim 1, wherein said peptide motif has an amino acid sequence selected from the group consisting of SNN, NSN, NNS, TNN, NTN, and NNT.

3. The biologically active protein conjugate of claim 1, wherein said amino acid extension is situated at the N-terminus with respect to said biologically active polypeptide, is situated at the C-terminus with respect to said biologically active polypeptide, or is situated at both the N- and C-termini with respect to said biologically active polypeptide.

4. The biologically active protein conjugate of claim 1, wherein said interferon is selected from the group consisting of a beta-interferon (SEQ ID NO:2468) and a gamma-interferon (SEQ ID NO:2470).

5. The biologically active protein conjugate of claim 1, wherein said biologically protein conjugate further comprises a leader sequence.

6. The biologically active protein conjugate of claim 5, wherein the leader sequence is the Schizosaccharomyces pome acid phosphatase (PHO) leader sequence (amino acid residues 1 to 18 of SEQ ID NO:2450).

7. The biologically active protein conjugate of claim 1, wherein said biologically active protein conjugate further comprises a linker.

8. A composition comprising the biologically active protein conjugate of claim 1 and a pharmaceutically effective carrier.