NOVEL PEPTIDES

Abstract: Oligopeptides which comprise amino acid sequences that are recognized and proteolytically cleaved by free prostate specific antigen (PSA) are described. Also described are assays which comprise such oligopeptides useful for determining free PSA protease activity in vitro and in vivo. Therapeutic agents which comprise conjugates of such oligopeptides and known cytotoxic agents are also described.

Description: ΉTLE OF THE INVENTION NOVEL PEPTIDES RELATED APPLICATION The present patent application is a Continuation-in-Part application of copending application Serial No. 08/404,833, filed March 15, 1995, which itself is a Continuation-in-Part apphcation of copending application Serial No. 08/267,092, filed June 28, 1994. BACKGROUND OF THE INVENTION In 1994 cancer of the prostate gland is expected to be diagnosed in 200,000 men in the U.S. and 38,000 American males will die from this disease (Garnick, M.B. (1994). The Dilemmas of Prostate Cancer. Scientific American, April:72-81). Thus, prostate cancer is the most frequently diagnosed malignancy (other than that of the skin) in U.S. men and the second leading cause of cancer-related deaths (behind lung cancer) in that group. Prostate specific Antigen (PSA) is a single chain 33 kDa glycoprotein that is produced almost exclusively by the human prostate epithelium and occurs at levels of 0.5 to 2.0 mg/ml in human seminal fluid (Nadji, M., Taber, S.Z., Castro, A., et al. (1981) Cancer 48:1229;Papsidero, L., Kuriyama, M., Wang, M., et al. (1981). JNCI 66:37; Qui, S.D., Young, C.Y.F., Bihartz, D.L., et al. (1990), J. Urol. 144:1550; Wang, M.C., Valenzuela, L.A., Murphy, G.P., et al. (1979). Invest. Urol. 17: 159). The single carbohydrate unit is attached at asparagine residue number 45 and accounts for 2 to 3 kDa of the total molecular mass. PSA is a protease with chymotrypsin-like specificity (Christensson, A., Laurell, C.B., Lilja, H. (1990). Eur. J. Biochem. 194:755-763). It has been shown that PSA is mainly responsible for dissolution of the gel structure formed at ejaculation by proteolysis of the major proteins in the sperm entrapping gel, Semenogelin I and Semenogelin II, and fibronectin (Lilja, H. (1985). J. Clin. Invest. 76:1899; Lilja, H., Oldbring, J., Rannevik, G., et al. (1987). J. Clin. Invest. 80:281; McGee, R.S., Herr, J.C. (1988). Biol. Reprod. 39:499). The PSA mediated proteolysis of the gel-forming proteins generates several soluble Semenogelin I and Semenogelin II fragments and soluble fibronectin fragments with liquefaction of the ejaculate and release of progressively motile spermatoza (Lilja, H., Laurell, C.B. (1984). Scand. J. Clin. Lab. Invest. 44:447; McGee, R.S., Herr, J.C. (1987). Biol. Reprod. 37:431). Furthermore, PSA may proteolytically degrade IGFBP- 3 (insulin-like growth factor binding protein 3) allowing IGF to stimulate specifically the growth of PSA secreting cells (Cohen et al., (1992) J. Clin. Endo. & Meta. 75:1046-1053). PSA complexed to alpha 1 - antichymotrypsin is the predominant molecular form of serum PSA and may account for up to 95% of the detected serum PSA (Christensson, A., Bjδrk, T., Nilsson, O., et al. (1993). J. Urol. 150:100-105; Lilja, H., Christensson, A., Dahlen, U. (1991). Clin. Chem. 37:1618-1625; Stenman, U.H., Leinoven, J., Alfthan, H., et al. (1991). Cancer Res. 51:222-226). The prostatic tissue (normal, benign hyperplastic, or malignant tissue) is implicated to predominantly release the mature, enzymatically active form of PSA, as this form is required for complex formation with alpha 1 - antichymotrypsin (Mast, A.E., Enghild, J J., Pizzo, S.V., et al. (1991). Biochemistry 30:1723-1730; Perlmutter, D.H., Glover, G.I., Rivetna, M., et al. (1990). Proc. Natl. Acad. Sci. USA 87:3753-3757). Therefore, in the microenvironment of prostatic PSA secreting cells the PSA is believed to be processed and secreted in its mature enzymatically active form not complexed to any inhibitory molecule. PSA also forms stable complexes with alpha 2 - macroglobulin, but as this results in encapsulation of PSA and complete loss of the PSA epitopes, the in vivo significance of this complex formation is unclear. A free, noncomplexed form of PSA constitutes a minor fraction of the serum PSA (Christensson, A., Bjδrk, T., Nilsson, O., et al. (1993). J. Urol. 150:100- 105; Lilja, H., Christensson, A., Dahlen, U. (1991). Clin. Chem. 37: 1618-1625). The size of this form of serum PSA is similar to that of PSA in seminal fluid (Lilja, H., Christensson, A., Dahlen, U. (1991). Clin. Chem. 37:1618-1625) but it is yet unknown as to whether the free form of serum PSA may be a zymogen; an internally cleaved, inactive form of mature PSA; or PSA manifesting enzyme activity. However, it seems unlikely that the free form of serum PSA manifests enzyme activity, since there is considerable (100 to 1000 fold) molar excess of both unreacted alpha 1 - antichymotrypsin and alpha 2 - macroglobulin in serum as compared with the detected serum levels of the free 33 kDa form of PSA (Christensson, A., Bjδrk, T., Nilsson, O., et al. (1993). J. Urol. 150:100-105; Lilja, H., Christensson, A., Dahlen, U. (1991). Clin. Chem. 37:1618-1625). Serum measurements of PSA are useful for monitoring the treatment of adenocarcinoma of the prostate (Duffy, M.S. (1989). Ann. Clin. Biochem. 26:379-387; Brawer, M.K. and Lange, P.H. (1989). Urol. Suppl. 5:11-16; Hara, M. and Kimura, H. (1989). J. Lab. Clin. Med. 113:541-548), although above normal serum concentrations of PSA have also been reported in benign prostatic hyperplasia and subsequent to surgical trauma of the prostate (Lilja, H., Christensson, A., Dahlen, U. (1991). Clin. Chem. 37:1618-1625). Prostate metastases are also known to secrete immunologically reactive PSA since serum PSA is detectable at high levels in prostatectomized patients showing widespread metatstatic prostate cancer (Ford, T.F., Butcher, D.N., Masters, R.W., et al. (1985). Brit. J. Urology 57:50-55). Therefore, a cytotoxic compound that could be activated by the proteolytic activity of PSA should be prostate cell specific as well as specific for PSA secreting prostate metastases. Accordingly, it is the object of this invention to provide novel oligopeptides which selectively are enzymatically cleaved by active free prostate specific antigen (PSA). It is also the object of this invention to provide a quantitative assay for enzymatically active PSA which incorporates those novel oligopeptides. It is further the object of this invention to provide a novel anti-cancer composition useful for the treatment of prostate cancer which comprises those novel oligopeptides in conjugation with a cytotoxic agent. Another object of this invention is to provide a method of treating prostate cancer which comprises administration of novel anti- cancer composition. 5 SUMMARY OF THE INVENTION The several points of cleavage where semenogelin I is selectively proteolytically cleaved by free PSA have been identified. Oligopeptides which comprise the amino acid sequences that are i o recognized and proteolytically cleaved by free prostate specific antigen (PSA) are described. Such oligopeptides are useful in assays which can determine the free PSA protease activity in vitro and in vivo. Furthermore, such oligopeptides may be incorporated into therapeutic agents which comprise conjugates of such oligopeptides and known 15 cytotoxic agents and which are useful in the treatment of prostatic cancer. BRIEF DESCRIPTION OF THE FIGURES FIGURES la and lb: Primary Amino Acid Sequence of Semenogelin I: 20 The primary amino acid sequence of Semenogelin I is shown. (SEQ.ID.NO.: 1) The PSA proteolytic cleavage sites ("CS") are shown (numbered in order of the relative affinity of a site towards PSA hydrolysis) and the protein fragments are numbered sequentially starting at the amino terminus. 25 FIGURE 2: Cleavage Affinity of Synthetic Oligopeptides: A nested set of synthetic oligopeptides was prepared and the oligopeptides were digested with enzymatically active free PSA for various times. The results are shown in Table 2. ND = not determined. 0 The single letter code for amino acids is used: A=Ala, E=Glu, G=Gly, H=His, I=Ile, K=Lys, L=Leu, N=Asn, Q=Gln, R=Arg, S=Ser, T=Thr, Y=Tyr. FIGURES 3a and 3b: Cleavage Affinity of Synthetic Oligopeptides: Synthetic oligopeptides were prepared and the oligopeptides were digested with enzymatically active free PSA for four (4) hours. The percentage of the oligopeptide that is cleaved in this period of time is listed. The results are shown in Table 4. FIGURE 4: Cytotoxicity Data ofNon-cleavable Oligopeptide- Doxorubicin Conjugates: The data of the figure shows comparative cytotoxicity of doxorubicin and a conjugate of doxorubicin covalently bound to an oligopeptide (Compound 12d) that does not contain the free PSA proteolytic cleavage site. The IC50 for doxorubicin is 0.3 μM, while the acetylated oligopeptide modified doxorubicin has an IC50 that has been reduced by greater than 300 fold. This conjugate had no HPLC detectable contamination with unmodified doxorubicin. The oligopeptide alone had no detectable cell killing activity. FIGURE 5: Cleavage Affinity of Oligopeptides in Conjugation with Doxorubicin by Free PSA In Vitro: Oligopeptides-doxorubicin conjugates were prepared and the conjugates were digested with enzymatically active free PSA for four (4) hours. The percentage conjugate that is enzymatically cleaved in the oligopeptide in this period of time is listed. The results are shown in Table 5. FIGURE 6: Cleavage Affinity of Oligopeptides in Conjugation with Doxorubicin in Cell Conditioned Media: Oligopeptides-doxorubicin conjugates were reacted for four (4) hours with cell culture media that had been conditioned by exposure to LNCaP cells (which are known to secrete free PSA) or DuPRO cell (which do not secrete free PSA). The percentage conjugate that is enzymatically cleaved in the oligopeptide in this period of time is listed. The results are shown in Table 6. FIGURE 7: Cytotoxicity Data of Cleavable Oligopeptide-Doxorubicin Conjugates: The data in Table 7 shows cytotoxicity (as IC50) of conjugates of doxorubicin covalently bound to an oligopeptide that contain a free PSA proteolytic cleavage site against a cancer cell line that is known to secrete free PSA. Also shown for selected conjugates is the cytotoxicity of the conjugate against a cell line (DuPRO) which does not secrete free PSA. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel oligopeptides which are specifically recognized by the free prostate specific antigen (PSA) and are capable of being proteolytically cleaved by the enzymatic activity of the free prostate specific antigen. Such oligopeptides include oligomers that comprise an amino acid sequence selected from: a) AsnLysIleSerTyrGln|Ser (SEQ.ID.NO.: 13), b) LysIleSerTyrGln|Ser (SEQ.ID.NO.: 14), c) GlyGluAsnGlyValGlnLysAspValSerGlnXaaSerIleTyr|SerGlnThrGlu (SEQ.ID.NO.: 15) , d) GlyLysGlyIleSerSerGlnTyr|SerAsnThrGluGluArgLeu (SEQ.ID.NO.: 2), e) AsnLysIleSerTyrTyr|Ser (SEQ.ID.NO.: 127), f) AsnLysAlaSerTyrGln|Ser (SEQ.ID.NO.: 128), g) SerTyrGln|SerSer (SEQ.ID.NO.: 129); h) LysTyrGln|SerSer (SEQ.ID.NO.: 140); and i) hArgTyrGln|SerSer (SEQ.ID.NO.: 141); wherein hArg is homoarginine and Xaa is any natural amino acid. In an embodiment of the instant invention, the oligopeptides include ohgomers that comprise an amino acid sequence that is selected from: a) AsnLysIleSerTyrGlnlSerSer (SEQ.ID.NO.: 16), b) AsnLysIleSerTyrGlnlSerAla (SEQ.ID.NO.: 130), c) AsnLysIleSerTyrGlnlSerSerSer (SEQ.ID.NO.: 17), d) AlaAsnLysIleSerTyrGlnlSerSerSer (SEQ.ID.NO.: 18), e) LysIleSerTyrGlnlSerSerSerThrGlu (SEQ.ID.NO.: 19), f) GlyGluAsnGlyValGlnLysAspValSerGlnArgSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 4), g) GlyGluAsnGlyValGlnLysAspValSerGlnSerSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 5), h) AlaAsnLysIleSerTyrTyrlSer (SEQ.ID.NO.: 131), i) AlaAsnLysAlaSerTyrGlnlSer (SEQ.ID.NO.: 132), j) SerTyrGlnlSerSerThr (SEQ.ID.NO.: 133), k) SerTyrGlnlSerSerSer (SEQ.ID.NO.: 134), 1) LysTyrGlnlSerSerSer (SEQ.ID.NO.: 142), m) hArgTyrGlnlSerSerSer (SEQ.ID.NO.: 143), and n) SerTyrGlnlSerSerLeu (SEQ.ID.NO.: 135). In a more preferred embodiment of the instant invention, the oligopeptides include ohgomers that comprise an amino acid sequence that is selected from: a) AsnLysIleSerTyrGln ISerSerSerThr (SEQ.ID.NO.: 10), b) AlaAsnLysIleSerTyrGlnlSerAla (SEQ.ID.NO.: 136), c) AsnLysIleSerTyrGlnlSerSerSerThrGlu (SEQ.ID.NO.:3 ), d) AlaAsnLysIleSerTyrGlnlSerSerSerThrGlu (SEQ.ID.NO.: 11), e) GlyGluAsnGlyValGlnLysAspValSerGlnArgSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 4), f) AlaAsnLysIleSerTyrTyrlSerSer (SEQ.ID.NO.: 137), g) AlaAsnLysIleSerTyrTyrlSerAla (SEQ.ID.NO.: 138), h) AlaAsnLysAlaSerTyrGlnlSerAla (SEQ.ID.NO.: 139), i) AlaSerTyrGlnlSerSerLeu (SEQ.ID.NO.: 94). In a further embodiment of the instant invention, the oligopeptides include ohgomers that comprise an amino acid sequence that is selected from: a) GlyArgLysAlaAsnLysIleSerTyrGlnlSerSerSerThrGluGluArgArg LeuHisTyr GlyGluAsnGly (SEQ.ID.NO.: 6). The phrase "ohgomers that comprise an amino acid sequence" as used hereinabove, and elsewhere in the Detailed Description of the Invention, describes ohgomers of from about 6 to about 100 amino acids residues which include in their amino acid sequence the specific amino acid sequence decribed and which are therefore proteolytically cleaved within the amino acid sequence described by free PSA. Thus, for example, the following oligomer: GlnLeuAspAsnLysIleSerTyrGlnlSerSerSerThrHisGlnSerSer (SEQ.ID.NO.: 20) comprises the amino acid sequence: AsnLysIleSerTyrGlnlSerSerSerThr (SEQ.ID.NO.: 10) and would therefore come within the instant invention. It is understood that such oligomers do not include semenogelin I and semenogelin II. It is also understood that the instant invention includes oligomers wherein the N-terminus amino acid or the C-terminus amino acid, or both terminus amino acids are modified. Such modifications include, but are not limited to, acylation of the amine group at the N- terminus and formation of an amide to replace the carboxylic acid at the C-terminus. Addition of such moieties may be performed during solid- phase synthesis of the oligomer; thus, attachment of the C-terminus amino acid to a solid phase resin may be through an amine which results in an amide moiety upon acidic cleavage of the oligomer from the resin. Thus the following compounds are considered "oligomers that comprise an amino acid sequence" as used hereinabove and are meant to be illustrative and are not limiting: AlaAsnLysIleSerTyrGlnlSerSerSerThrGlu-amide (SEQ.ID.NO.: 11) Ac-AlaAsnLysIleSerTyrGlnlSerSerSerThrLeu (SEQ.ID.NO.: 70) Ac-AlaAsnLysIleSerTyrGlnlSerSerSerThrGlu-amide (SEQ.ID.NO.: 11) Ac-AJaAsnLysIleSerTyrGlnlSerSerSerThrLeu-amide (SEQ.ID.NO.: 70) Ac-AlaAsnLysIleSerTyrGlnlSerAlaSerThrGlu-amide (SEQ.ID.NO.: 73) Ac-AlaAsnLysIleSerTyrGlnlSerSerLysThrGlu-amide (SEQ.ID.NO.: 74) Ac-AlaAsnLysIleSerTyrGlnlSerSerThrGlu-amide (SEQ.ID.NO.: 75) Ac-AlaAsriysIleSerTyrGlnlSerSerGlnTlirGlu-aniide (SEQ.ID.NO.: 78) Ac-AlaAsnLysIleSerTyrGlnlSerAlaLysThrGlu-amide (SEQ.ID.NO.:79) Ac-AlaAsnLysIleSerTyrGlnlSerThrGlu-amide (SEQ.ID.NO.: 81) Ac-AlaAsnLysSerTyrGlnlSerSerThrGlu-amide (SEQ.ID.NO.: 82) Ac-AJaAsrLLysAlaSerTyrGlnlSerAJaSerThrGlu-amide (SEQ.ID.NO. : 84) Ac-AlaAsnGluIleSerTyrGlnlSerAlaSerThrGlu-amide (SEQ.ID.NO.: 85) Ac-AsnLysIleSerTyrGlnlSerSer-amide (SEQ.ID.NO.: 16) Ac-LysIleSerTyrGlnlSerSer-amide (SEQ.ID.NO.: 86) Ac-SerTyrGlnlSerSerThrGlu-arnide (SEQ.ID.NO.: 87) Ac-AlaSerTyrGlnlSerSerThrGlu-amide (SEQ.ID.NO.: 89) Ac-AlaAsnLysIleSerTyrTyrlSerSerSerThrGlu-amide (SEQ.ID.NO.: 92) Ac-AlaAsnLysIleSerTyrTyrlSerAlaSerThrGlu-amide (SEQ.ID.NO.: 93) Ac-AlaSerTyrGlnlSerSerLeu-amide (SEQ.ID.NO.: 94) Ac-AlaAsnSerTyrGlnlSerSerSerThrGlu-amide (SEQ.ID.NO.: 95) Ac-AlaSerTyrGlnlSerSerSerThrGlu-amide (SEQ.ID.NO.: 96) Ac-SerTyrGlnlSerSerSerThrGlu-amide (SEQ.ID.NO.: 97) Ac-AlaAsnLysAlaSerTyrGlnlSerAlaSerCys-amide (SEQ.ID.NO.: 98) A person of ordinary skill in the peptide chemistry art would readily appreciate that certain amino acids in a biologically active oligopeptide may be replaced by other homologous, isosteric and/or isoelectronic amino acids wherein the biological activity of the original oligopeptide has been conserved in the modified oligopeptide. The following list of amino acid replacements is meant to be illustrative and is not limiting: Thus, for example, the following oligopeptides may be synthesized by techniques well known to persons of ordinary skill in the art and would be expected to be proteolytically cleaved by free PSA: AsnArglleSerTyrGlnlSer (SEQ.ID.NO.: 21) AsnLysValSerTyrGlnlSer (SEQ.ID.NO.: 22) AsnLysMetSerTyrGlnlSerSer (SEQ.ID.NO.: 23) AsnLysLeuSerTyrGln ISerSer (SEQ.ID.NO.: 24) AsnLysIleThrTyrGlnlSerSerSer (SEQ.ID.NO.: 25) AsnLysIleSerPheGlnlSerSerSer (SEQ.ID.NO.: 26) AsnLysIleSerTrpGlnlSerSerSerThr (SEQ.ID.NO.: 27) AsnLysIleSerTyrAsnlSerSerSerThr (SEQ.ID.NO.: 28) AsnLysπeSerTyrGlnlThrSerSerThr (SEQ.ID.NO.: 29) AsnLysIleSerTyrGlnlSer (SEQ.ID.NO.: 30) GlnLysIleSerTyrGlnlSerSer (SEQ.ID.NO.: 31) AsnArglleThrTyrGlnlSerSerSer (SEQ.ID.NO.: 32) AsnArglleSerPheGlnlSerSerSerThr (SEQ.ID.NO.: 33) AsnArglleSerTrpGlnlSerSerSerThr (SEQ.ID.NO.: 35) AsnArglleSerTyrGlnlThrSerSerThr (SEQ.ID.NO.: 36) AsnLysIleThrTyrGlnlThrSerSerThr (SEQ.ID.NO.: 37) AsnLysLeuSerTyrGlnlThrSerSerThr (SEQ.ID.NO.: 38) GlnLysLeuSerTyrGlnlSerSerSerThr (SEQ.ID.NO.: 39) AsnArgLeuSerTyrGlnlThrSerSerThr (SEQ.ID.NO.: 40) AsnLysValSerPheGlnlSerSerSerThr (SEQ.ID.NO.: 41) AsnArgValSerTrpGlnlSerSerSerThr (SEQ.ID.NO.: 42) GlnLysValSerTyrGlnlSerSerSerThr (SEQ.ID.NO.: 43) GlnLysIleSerTyrGlnlThrSerSerThr (SEQ.ID.NO.: 34) AsnLysIleSerTyrGlnlSerSerSerThr (SEQ.ID.NO.: 44) Similarly, the following oligopeptides may be synthesized by techniques well known to persons of ordinary skill in the art and would be expected to be proteolytically cleaved by free PSA: GlyGluGlnGlyValGlnLysAspValSerGlnSerSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 45) , GlyGluAsnGlyLeuGlnLysAspValSerGlnSerSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 47) , GlyGluAsnGlyValAsnLysAspValSerGlnSerSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 48) , GlyGluAsnGlyValGlnArgAspValSerGlnArgSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 49) , GlyGluAsnGlyValGlrX-ysAspValSerGlnLysSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 50) , GlyGluAsnGlyValGlnLysAspLeuSerGlnThrSerlleTyrlSerGlnThrGlu (SEQ.ID.NO.: 51) , GlyGluAsnGlyValGlnLysAspValSerGlnSerSerllePhelSerGlnThrGlu (SEQ.ID.NO.: 52) , GlyGluAsnGlyValGlnLysAspMetSerGlnSerSerlleTyrlThrGlnThrGlu (SEQ.ID.NO.: 53) , GlyGluAsnGlyValGlriLysAspValSerGlnArgSerlleTyrlThrGlnThrGlu (SEQ.ID.NO.: 54) , GlyGluAsnGlyValGlnLysAspValSerGlnSerSerlleTyrlSerGlnSerGlu (SEQ.ID.NO.: 55) , GlyGluAsnGlyValGlnLysAspValSerGlnArgSerlleTyrlSerAsnThrGlu (SEQ.ID.NO.: 56), GlyLysAlalleSerSerGlnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO. 57), GlyArgGlylleSerSerGlnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO. : 59), GlyLysGlylleThrSerGlnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO. : 60), GlyLysGlylleSerThrGlnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO.: 61), GlyLysGlylleSerSerAsnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO.: 62), AlaLysGlylleSerSerGlnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO. : 63), GlyLysGlylleSerSerGlnPhelSerAsnThrGluGluArgLeu (SEQ.ID.NO. : 64), GlyLysGlylleSerSerGlnTyrlThrAsnThrGluGluArgLeu (SEQ.ID.NO. : 65), GlyLysGlylleSerSerGlnTyrlSerAsnSerGluGluArgLeu (SEQ.ID.NO.: 58), and GlyLysGlylleSerSerGlnTyrlSerAsnThrAspGluArgLeu (SEQ.ID.NO.: 46); and the like. The inclusion of the symbol "I" within an a ino acid sequence indicates the point within that sequence where the oligopeptide is proteolytically cleaved by free PSA. The invention also concerns a method for assaying proteolytic free PSA activity in a composition. This is an important aspect of the invention in that such an assay system provides one with the ability to measure quantitatively the amount of free PSA present in certain physiological fluids and tissues. Such an assay will also provide not only the ability to follow isolation and purification of free PSA, but also is a basis for a screening assay for inhibitors of the proteolytic activity of free PSA. The assay method generally includes simply determining the ability of a composition suspected of containing enzymatically active free PSA to proteolytically cleave the oligopeptide. Typically, the assay protocol is carried out using one of the oligopeptides described hereinabove. However, one may find a particular benefit in construction of an assay wherein the oligopeptide containing the cleavage site is labeled so that one can measure the appearance of such a label, for example, a radioactive label, in both the uncleaved oligopeptide and the portion of the oligopeptide remaining after cleavage which contains the label. The instant invention further relates to a method for identifying compounds (hereinafter referred to as candidate compounds) that will inhibit the proteolytic activity of free PSA. It is contemplated that this screening technique will prove useful in the general identification of any candidate compound that will serve such as an inhibitory purpose, whether or not the candidate compound is proteinaceous or peptidyl in structure. Thus, the present invention is also directed to a method for deteπriining the ability of a test substance to inhibit the proteolytic activity of free PSA, the method which comprises: (a) reacting a substrate, wherein the substrate comprises a sequence of amino acids that is recognized and selectively proteolytically cleaved by free prostate specific antigen, with free prostate specific antigen in the presence of a test substance; and (b) detecting whether the substrate has been cleaved, in which the ability of the test substance to inhibit proteolytic activity of prostate specific antigen is indicated by a decrease in the cleavage of the substrate as compared to the cleavage of the substrate in the absence of the test substance. The candidate screening assay is quite simple to set up and perform, and is related in many ways to the assay discussed above for determining proteolytic activity. Thus, after obtaining a relatively purified preparation of free PSA, one will desire to simply admix a test substance with the proteolytic preparation, preferably under conditions which would allow the PSA to perform its cleavage function but for inclusion of a inhibitory substance. Thus, for example, one will typically desire to include within the admixture an amount of a known oligopeptide having a PSA specific cleavage site, such as those oligopeptides described hereinabove. In this fashion, one can measure the ability of the test substance to reduce cleavage of the oligopeptide relatively in the presence of the test substance. Accordingly, one will desire to measure or otherwise determine the activity of the free PSA in the absence of the added test substance relative to the activity in the presence of the test substance in order to assess the relative inhibitory capability of the test substance. The instant invention also relates to novel anti-cancer compositions useful for the treatment of prostate cancer. Such compositions comprise the oligopeptides of the instant invention covalently bonded directly, or through a chemical linker, to a cytotoxic agent. Such a combination of an oligopeptide and cytotoxic agent may be termed a conjugate. Ideally, the cytotoxic activity of the cytotoxic agent is greatly reduced or absent when the oligopeptide containing the PSA proteolytic cleavage site is bonded directly, or through a chemical linker, to the cytotoxic agent and is intact. Also ideally, the cytotoxic activity of the cytotoxic agent increases significantly or returns to the activity of the unmodified cytotoxic agent upon proteolytic cleavage of the attached oligopeptide at the cleavage site. While it is not necessary for practicing this aspect of the invention, the most preferred embodiment of this aspect of the invention is a conjugate wherein the oligopeptide, and the chemical Unker if present, are detached from the cytotoxic agent by the proteolytic activity of the free PSA and any other native proteolytic enzymes present in the tissue proximity, thereby releasing unmodified cytotoxic agent into the physiological environment at the place of proteolytic cleavage. It is understood that the oligopeptide of the instant invention that is conjugated to the cytotoxic agent, whether through a direct covalent bond or through a chemical linker, does not need to be the oligopeptide that has the greatest recognition by free PSA and is most readily proteolytically cleaved by free PSA. Thus, the oligopeptide that is selected for incorporation in such an anti-cancer composition will be chosen both for its selective, proteolytic cleavage by free PSA and for the cytotoxic activity of the cytotoxic agent-proteolytic residue conjugate (or, in what is felt to be an ideal situation, the unmodified cytotoxic agent) which results from such a cleavage. Because the conjugates of the invention can be used for modifying a given biological response, cytotoxic agent is not to be construed as limited to classical chemical therapeutic agents. For example, the cytotoxic agent may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a protein such as tumor necrosis factor, α-interferon, β-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator; or, biological response modifiers such as, for example, lymphokines, interleukin-1 ("IL-1"), interleukin-2 ("IL-2"), interleukin-6 ("IL-6"), granulocyte macrophage colony stimulating factor ("GM- CSF"), granulocyte colony stimulating factor ("G-CSF"), or other growth factors. The preferred cytotoxic agents include, in general, alkylating agents, antiproliferative agents, tubulin binding agents and the like. Preferred classes of cytotoxic agents include, for example, the anthracycline family of drugs, the vinca drugs, the mitomycins, the bleomycins, the cytotoxic nucleosides, the pteridine family of drugs, diynenes, and the podophyllotoxins. Particularly useful members of those classes include, for example, doxorubicin, carminomycin, daunorubicin, aminopterin, methotrexate, methopterin, dichloro- methotrexate, mitomycin C, porfiromycin, 5-fluorouracil, 6- mercaptopurine, cytosine arabinoside, podophyllotoxin, or podo- phyllotoxin derivatives such as etoposide or etoposide phosphate, melphalan, vinblastine, vincristine, leurosidine, vindesine, leurosine and the like. Other useful cytotoxic agents include estramustine, cisplatin and cyclophosphamide. One skilled in the art may make chemical modifications to the desired compound in order to make reactions of that compound more convenient for purposes of preparing conjugates of the invention. A highly preferred group of cytotoxic agents for the present invention include drugs of the following formulae: THE METHOTREXATE GROUP OF FORMULA.1.: (1) in which Rl2 is amino or hydroxy; R7 is hydrogen or methyl; R8 is hydrogen, fluoro, chloro, bromo or iodo; R9 is hydroxy or a moiety which completes a salt of the carboxylic acid; THE MITOMYCIN GROUP OF FORMULA (2): (2) in which RlO is hydrogen or methyl; THE BLEOMYCIN GROUP OF FORMULA (3) (3) in which Rll is hydroxy, amino, C1-C3 all ylamino, di(Cl-C3 alkyl)amino, C4-C6 polymethylene amino, NH + II -NHCH 2 CH 2 CH 2 S-CH 3 ; or -NHCH 2 CH 2 CH 2 CH 2 NH-C-NH 2 ; I CH 3 MELPHALAN OF FORMULA (4 : (4) 6-MERCAPTOPURINE OF FORMULA (5): (5) A CYTOSINE ARABINOSIDE OF FORMULA (6): (6) THE PODOPHYLLOTOXINS OF FORMULAE : in which Rl3 is hydrogen or methyl; Rl4 is methyl or thienyl; or a phosphate salt thereof; THEVINCAALKALOIDGROUPOFDRUGSOFFORMULA(8.: (8) in which Rl5 is H, CH3 or CHO; when R 17 and Rl8 are taken singly; Rl8 is H, and one of Rl6 and Ri 7 is ethyl and the other is H or OH; when Rl7 and R 18 are taken together with the carbons to which they are attached, they form an oxirane ring in which case Rl6 i s ethyl; R19 IS hydrogen, (C1-C3 alkyl)-CO, or chlorosubstituted (C1-C3 alkyl)-CO; DIFLUORONUCLEOSIDES OF FORMULA (9 : (9) in which R21 is a base of one of the formulae: in which R22 is hydrogen, methyl, bromo, fluoro, chloro or iodo; R23 is -OH or -NH2; R24 is hydrogen, bromo, chloro or iodo; or, THE ANTHRACYCLINES ANΗBIOTICS OF FORMULA .10.: (10) wherein Rl is -CH3, -CH20H, -CH20CO(CH2)3CH3, or -CH2θCOCH(OC2H5)2; R3 is -OCH3, -OH or -H; R4 is -NH2, -NHCOCF3, 4-moφhohnyl, 3-cyano-4- moφholinyl, 1-piperidinyl, 4-methoxy-l-piperidinyl, benzylamine, dibenzylamine, cyanomemylamine, or 1- cyano-2-methoxyethyl amine; R5 is -OH -OTHP or -H; and R6 is -OH or -H provided that R6 is not -OH when R-5 is -OH or -OTHP. ESTRAMUSTINE d l (11) CYCLOPHOSPHAMIDE (12. 12 The most highly preferred drugs are the anthracycline antiobiotic agents of Formula (10), described previously. One skilled in the art understands that this structural formula includes compounds which are drugs, or are derivatives of drugs, which have acquired in the art different generic or trivial names. Table 1, which follows, represents a number of anthracycline drugs and their generic or trivial names and which are especially preferred for use in the present invention. Table 1 Compound l El daunorubicin a CH3 OCH3 doxorubicin 0 CH20H OCH3 detorubicin CH20COCH(OC2H5)2 OCH3 carminomycin CH3 OH idarubicin CH3 H epirubicin CH20H OCH3 esorubicin CH2OH OCH3 TΗP CH20H OCH3 AD-32 CH20CO(CH2)3CH3 OCH3 a "daunomycin" is an alternative name for daunorubicin b"adriamycin" is an alternative name for doxorubicin Of the compounds shown in Table 1, the most highly preferred drug is doxorubicin. Doxorubicin (also referred to herein as "DOX") is that anthracycline of Formula (10) in which Rl is -CH20H, R3 is -OCH3, R4 is -NH2, R5 is -OH, and R6 is -H. The oligopeptides, peptide subunits and peptide derivatives (also termed "peptides") of the present invention can be synthesized from their constituent amino acids by conventional peptide synthesis techniques, preferably by solid-phase technology. The peptides are then purified by reverse-phase high performance liquid chromatography (HPLC). Standard methods of peptide synthesis are disclosed, for example, in the following works: Schroeder et al, "The Peptides", Vol. I, Academic Press 1965; Bodansky et al, "Peptide Synthesis", Interscience Publishers, 1966; McOmie (ed.) "Protective Groups in Organic Chemistry", Plenum Press, 1973; Barany et al, "The Peptides: Analysis, Synthesis, Biology" 2, Chapter 1, Academic Press, 1980, and Stewart et al., "Solid Phase Peptide Synthesis", Second Edition, Pierce Chemical Company, 1984. The teachings of these works are hereby incoφorated by reference. The conjugates of the instant invention which comprise the oligopeptide containing the PSA cleavage site and a cytotoxic agent may similarly be synthesized by techniques well known in the medicinal chemistry art. For example, a free amine moiety on the cytotoxic agent may be covalently attached to the oligopeptide at the carboxyl terminus such that an amide bond is formed. Similarly, an amide bond may be formed by covalently coupling an amine moiety of the oligopeptide and a carboxyl moiety of the cytotoxic agent. For these puφoses a reagent such as a combination of 2-(l H-benzotriazol-1-yl)- 1,3,3- tetramethyluronium hexafluorophosphate (known as HBTU) and 1- hyroxybenzotriazole hydrate (known as HOBT), dicyclohexyl- carbodiimide (DCC), N-ethyl-N-(3-dimethylaminopropyl)- carbodiimide (EDC), diphenylphosphorylazide (DPP A), benzotriazol-1-yl-oxy-tris- (dimethylamino)phosphonium hexafluorophosphate (BOP) and the like may be utilized. Furthermore, the instant conjugate may be formed by a non- peptidyl bond between the PSA cleavage site and a cytotoxic agent. For example, the cytotoxic agent may be covalently attached to the carboxyl terminus of the oligopeptide via a hydroxyl moiety on the cytotoxic agent, thereby forming an ester linkage. For this puφose a reagent such as a combination of HBTU and HOBT, a combination of BOP and imidazole, a combination of DCC and DMAP, and the like may be utilized. The carboxylic acid may also be activated by forming the nitro- phenyl ester or the like and reacted in the presence of DBU (1,8- diazabicyclo [5 ,4,0]undec-7-ene. The instant conjugate may also be formed by attachment of the oligopeptide to the cytotoxic agent via a linker unit. Such hnker units include, for example, a biscarbonyl alkyl diradical whereby an amine moiety on the cytotoxic agent is connected with the linker unit to form an amide bond and the amino terminus of the oligopeptide is connected with the other end of the linker unit also forming an amide bond. Other such linker units which are stable to the physiological environment when not in the presence of free PSA, but are cleavable upon the cleavage of the PSA proteolytic cleavage site, are also envisioned. Furthermore, hnker units may be utilized that, upon cleavage of the PSA proteolytic cleavage site, remain attached to the cytotoxic agent but do not significantly decrease the cytotoxic activity of such a post-cleavage cytotoxic agent derivative when compared with an unmodified cytotoxic agent. One skilled in the art understands that in the synthesis of compounds of the invention, one may need to protect or block various reactive functionalities on the starting compounds and intermediates while a desired reaction is carried out on other portions of the molecule. After the desired reactions are complete, or at any desired time, normally such protecting groups will be removed by, for example, hydrolytic or hydrogenolytic means. Such protection and deprotection steps are conventional in organic chemistry. One skilled in the art is referred to Protective Groups in Organic Chemistry. McOmie, ed., Plenum Press, NY, NY (1973); and, Protective Groups in Organic Synthesis. Greene, ed., John Wiley & Sons, NY, NY (1981) for the teaching of protective groups which may be useful in the preparation of compounds of the present invention. By way of example only, useful amino-protecting groups may include, for example, Cl-Cio alkanoyl groups such as formyl, acetyl, dichloroacetyl, propionyl, hexanoyl, 3,3-diethylhexanoyl, γ- chlorobutryl, and the like; Cl-Cio alkoxycarbonyl and C5-C15 aryloxycarbonyl groups such as tert-butoxycarbonyl, benzyloxycarbonyl, allyloxycarbonyl, 4-nitrobenzyloxycarbonyl, fluorenylmethyloxycarbonyl and cinnamoyloxycarbonyl; halo-(Cl-Clθ)-alkoxycarbonyl such as 2,2,2-trichloroethoxycarbonyl; and C1-C15 arylalkyl and alkenyl group such as benzyl, phenethyl, allyl, trityl, and the like. Other commonly used amino-protecting groups are those in the form of enamines prepared with β-keto-esters such as methyl or ethyl acetoacetate. Useful carboxy-protecting groups may include, for example, Cl-Cio alkyl groups such as methyl, tert-butyl, decyl; halo-Ci-Clθ alkyl such as 2,2,2-trichloroethyl, and 2-iodoethyl; C5-C15 arylalkyl such as benzyl, 4-methoxybenzyl, 4-nitrobenzyl, triphenylmethyl, diphenyl- methyl; Cl-Cio alkanoyloxymethyl such as acetoxymethyl, propionoxymethyl and the like; and groups such as phenacyl, 4- halophenacyl, allyl, dimethylallyl, tri-(Cl-C3 alkyl)silyl, such as trimethylsilyl, β-p-toluenesulfonylethyl, β-p-nitrophenyl-thioethyl, 2,4,6- trimethylbenzyl, β-methylthioethyl, phthalimidomethyl, 2,4-dinitro- phenylsulphenyl, 2-nitrobenzhydryl and related groups. Similarly, useful hydroxy protecting groups may include, for example, the formyl group, the chloroacetyl group, the benzyl group, the benzhydryl group, the trityl group, the 4-nitrobenzyl group, the trimethylsilyl group, the phenacyl group, the tert-butyl group, the methoxymethyl group, the tetrahydropyranyl group, and the like. With respect to the preferred embodiment of an oligopeptide combined with the anthracycline antibiotic doxorubicin, the following Reaction Schemes illustrate the synthsis of the conjugates of the instant invention. REACTION SCHEME REACTION SCHEME II OH REACTION SCHEME OH REACTION SCHEME IV OH REACTION SCHEME V OH Reaction Scheme VI illustrates preparation of conjugates of the oligopeptides of the instant invention and the vinca alkaloid cytotoxic agent vinblastine. Attachement of the N-terminus of the oligopeptide to vinblastine is illustrated (S.P. Kandukuri et al. J. Med. Chem. 28:1079- 1088 (1985)). However, conjugation of the oligopeptide at other positions and functional groups of vinblastine and at the C-terminus of the oligopeptide is also expected to provide compounds useful in the treatment of prostate cancer. It is also understood that conjugates may be prepared wherein the N-terminus of the oligopeptide of the instant invention is covalently attached to one cytotoxic agent, such as vinblastine, while the C-terminus is simultaneously attached to another cytotoxic agent, which is the same or different cytotoxic agent, such as doxorubicin. Such a polycytotoxic conjugate may offer advantages over a conjugate containing only one cytotoxic agent. REACTION SCHEME VI REACTION SCHEME VI e - C - NH 2 The oligopeptide-cytotoxic agent conjugate of the instant invention wherein the cytotoxic agent is the preferred cytotoxic agent doxorubicin may be described by the general formula I below: wherein: oligopeptide is an ohgopeptide which is specifically recognized by the free prostate specific antigen (PSA) and is capable of being proteolytically cleaved by the enzymatic activity of the free prostate specific antigen; XL is absent or is an amino acid selected from: a) phenylalanine, b) leucine, c) valine, d) isoleucine, e) (2-naphthyl)alanine, f) cyclohexylalanine, g) diphenylalanine, h) norvahne, and j) norleucine; R is hydrogen or -(C=0)Rl; and R is Cl-C6-alkyl or aryl. In a preferred embodiment of the oligopeptide-cytotoxic agent conjugate: oligopeptide is an oligomer that comprises an amino acid sequence selected from: a) AsnLysIleSerTyrGlnlSer (SEQ.ID.NO.: 13), b) LysIleSerTyrGlnlSer (SEQ.ID.NO.: 14), c) GlyGluAsnGlyValGlnLysAspValSerGlr_XaaSerIleTyrlSerGlnThrGlu (SEQ.ID.NO.: 15) , d) GlyLysGlylleSerSerGlnTyrlSerAsnThrGluGluArgLeu (SEQ.ID.NO.: 2), e) AsnLysIleSerTyrTyrlSer (SEQ.ID.NO.: 127), f) AsnLysAlaSerTyrGlnlSer (SEQ.ID.NO.: 128), g) SerTyrGlnlSerSer (SEQ.ID.NO.: 129), and h) hArgTyrGlnlSerSer (SEQ.ID.NO.: 141); wherein Xaa is any natural amino acid; XL is absent or is an amino acid selected from: a) leucine, b) isoleucine, c) norleucine, and d) valine; and R is acetyl, pivaloyl or benzoyl. The following compounds are specific examples of the oligopeptide-cytotoxic agent conjugate of the instant invention: wherein X is: H N— AsnLyslleSerTyrGlnSer— C— (SEQ.ID.NO.: 13), O H 2 N— AsnLyslleSerTyrGlnSerSer-c- (SEQ.ID.NO.: 16), II H 2 N— AsnLyslleSerTyrGlnSerSerSer -C— (SEQ.ID.NO.:17 ), II H 2 N— AsnLyslleSerTyrGlnSerSerSerThr -C- (SEQ.ID.NO..-10), H 2 N— AsnLyslleSerTyrGlnSerSerSerThrGlu -C- (SEQ.ID.NO.: 3), O II H 2 N— AlaAsnLyslleSerTyrGlnSerSerSerThrGlu -C- (SEQ.ID.NO.: 11), AcHN — AlaAsnLyslleSerTyrGlnSerSerSerThr-C - (SEQ.ID.NO.: 117), O II AcHN — AlaAsnLyslleSerTyrGlnSerSerSerThrLeu-C- (SEQ.ID.NO.: 70), O II AcHN — AlaAsnLysAlaSerTyrGlnSerAlaSerThrLeu-C- (SEQ.ID.NO.: 118), O II AcHN — AlaAsnLysAlaSerTyrGlnSerAlaSerLeu-C- (SEQ.ID.NO.: 119), O II AcHN — AlaAsnLysAlaSerTyrGlnSerSerSerl_eu-C- (SEQ.ID.NO.: 120), O II AcHN — AlaAsnLysAlaSerTyrGlnSerSerLeu-C- (SEQ.ID.NO.: 121). O II AcHN — SerTyrGlnSerSerSerLeu-C- (SEQ.ID.NO.: 144), O AcHN — hArgTyrGlnSerSerSerLeu-C- (SEQ.ID.NO.: 145). O II AcHN — LysTyrGlnSerSerSerLeu-C- (SEQ.ID.NO.: 124), or O II AcHN — LysTyrGlnSerSerNle -C- (SEQ.ID.NO.: 146). It is well known in the art, and understood in the instant invention, that peptidyl therapeutic agents such as the instant oligopeptide-cytotoxic agent conjugates preferably have the terminal amino moiety of any oligopeptide substituent protected with a suitable protecting group, such as acetyl, benzoyl, pivaloyl and the like. Such protection of the terminal amino group reduces or eliminates the enzymatic degradation of such peptidyl therapeutic agents by the action of exogenous amino peptidases which are present in the blood plasma of warm blooded animals. The ohgopeptide-cytotoxic agent conjugates of the invention are administered to the patient in the form of a pharmaceutical composition which comprises a conjugate of Formula (I) and a pharmaceutically acceptable carrier, excipient or diluent therefor. As used, "pharmaceutically acceptable" refers to those agents which are useful in the treatment or diagnosis of a warm-blooded animal including, for example, a human, equine, procine, bovine, murine, canine, feline, or other mammal, as well as an avian or other warm-blooded animal. The preferred mode of administration is parenterally, particularly by the intravenous, intramuscular, subcutaneous, intraperitoneal, or intralymphatic route. Such formulations can be prepared using carriers, diluents or excipients familiar to one skilled in the art. In this regard, See, e.g. Remington's Pharmaceutical Sciences. 16th ed., 1980, Mack Publishing Company, edited by Osol et al. Such compositions may include proteins, such as serum proteins, for example, human serum albumin, buffers or buffering substances such as phosphates, other salts, or electrolytes, and the like. Suitable diluents may include, for example, sterile water, isotonic saline, dilute aqueous dextrose, a polyhydric alcohol or mixtures of such alcohols, for example, glycerin, propylene glycol, polyethylene glycol and the like. The compositions may contain preservatives such as phenethyl alcohol, methyl and propyl parabens, thimerosal, and the like. If desired, the composition can include about 0.05 to about .20 percent by weight of an antioxidant such as sodium metabisulfite or sodium bisulfite. For intravenous administration, the composition preferably will be prepared so that the amount administered to the patient will be from about .01 to about 1 g of the conjugate. Preferably, the amount administered will be in the range of about .2 g to about 1 g of the conjugate. The conjugates of the invention are effective over a wide dosage range depending on factors such as the disease state to be treated or the biological effect to be modified, the manner in which the conjugate is administered, the age, weight and condition of the patient as well as other factors to be determined by the treating physician. Thus, the amount administered to any given patient must be determined on an individual basis. One skilled in the art will appreciate that although specific reagents and reaction conditions are outlined in the following examples, modification can be made which are meant to be encompassed by the spirit and scope of the invention. The following preparations and examples, therefore, are provided to further illustrate the invention, and are not hmiting. EXAMPLES EXAMPLE 1 Identification of the Semenogelin PSA Mediated Cleavage Site: Liquefaction of the seminal gel parallels proteolytic fragmentation of semenogelin I [Lilja, H., Laurell, C.B., (1984) Scand. J. Clin. Lab. Inves. 44, 447-452]. It is beheved that the proteolytic fragmentation of semenogelin is mainly due to the proteolytic activity of prostate-specific antigen [Lilja, H., (1985) J. Clin. Invest. 76, 1899-1903]. Utilizing the published sequence of semenogelin I [Lilja, H., Abrahamsson, P.A., Lundwall, A., (1989) J. of Biol. Chem. 264, 1894-1900] (Figure 1) we designed polymerase chain reaction primers to clone the semenogelin cDNA from a commercially available prostatic cDNA library (Clone- tech, Palo Alto, CA.). The purified semenogelin cDNA was placed into the bacterial expression vector pTAC [Linemeyer, D.L., Kelly, L.J., Minke, J.G., Gimenez-Gallego, G., DeSalvo, J. and Thomas, K.A., (1987) Bio Technology 5, 960-965]. The semenogehn cDNA was designed so that a tubulin epitope was placed at the carboxyl end of semenogelin protein.. The bacterially expressed semenogehn protein was purified on an anti-tubuhn antibody column. The purified semenogehn I protein was mixed with commercially prepared prostate-specific antigen (PSA) (York Biologicals International, Stony Brook, NY) in an 100 to 1 molar ratio (semenogehn I/PSA) in 12 mM Tris pH 8.0, 25 mM NaCl, 0.5 mM CaCl2, and incubated for various times. The digest was fractionated by polyacrylamide gel electrophoresis and transferred by electrophoresis to ProBlott filter paper (Applied Biosystems, Inc., Foster City, CA.) in CAPS buffer [Matsudaira, P., (1987) J. Biol. Chem. 252, 10035-10038]. The ProBlott filter paper was stained with coomassie blue to identify the novel PSA generated semenogelin I protein fragments. The novel fragments were cut out of the filter with a scalpel and submitted for sequence determination. After the proteolytic fragments were identified by variable time digestion, a 10 minute digestion reaction was performed. The affinity of PSA for the 5 potential cleavage sites in semenogelin I was determined to be as follows: site 349/350 > site 375/376 > site 289/290 = site 315/316 > site 159/160. The relative affinities were derived from the comassie blue staining intensity of each PSA generated peptide fragment. These intensities had approximate ratios of 3:1:0.6:0.3. EXAMPLE 2 Preparation of Oligopeptides which Comprise the PSA Mediated Cleavage Site: Oligopeptides were prepared by solid-phase synthesis, using a double coupling protocol for the introduction of amino acids on the Applied Biosystems model 430A automated peptide synthesizer. Deprotection and removal of the oligopeptide from the resin support were achieved by treatment with liquid hydrofluoric acid. The oligopeptides were purified by preparative high pressure liquid chromatography on reverse phase C18 silica columns using an aqueous 0.1% trifluoroacetic acid/acetonitrile gradient. Identity and homogeneity of the oligopeptides were confirmed by amino acid composition analysis, high pressure liquid chromatography, and fast atom bombardment mass spectral analysis. The ohgopeptides that were prepared by this method are shown in Figure 2. EXAMPLE 3 Assessment of the Recognition of Oligopeptides by Free PSA : The oligopeptides prepared as described in Example 2 were individually dissolved in PSA digestion buffer (12 mM tris(hydroxymethyl)- aminomethane pH8.0, 25 mM NaCl, 0.5 mM CaCl2) and the solution added to PSA at a molar ration of 100 to 1. The reaction is quenched after various reaction times by the addition of trifluoroacetic acid (TFA) to a final 1% (volume/volume). The quenched reaction was analyzed by HPLC on a reversed-phase C18 column using an aqueous 0.1%TFA/acetonitrile gradient. The results of the assessment are shown in Figure 2. Other oligopeptides prepared as described in Example 2 were tested in the same assay wherein the reaction was quenched at 4 hours. Those results of the assessment are shown in Figure 3. The removal of an asparagine residue from the amino terminus of the oligopeptide results in a significant loss of PSA mediated peptide hydrolysis, while the presence of a glutamic acid residue at the carboxyl end of the peptide appears not to be essential to recognition by PSA. EXAMPLE 4 Preparation of Non-cleavable Oligopeptide-Doxorubicin Conjugates: The derivatives of doxorubicin shown in Table 3 were prepared using the following general reaction: To a mixture of doxorubicin (Sigma) and the corresponding peptide (prepared by solid phase synthesis or commercially available (Sigma)) in DMSO was added HBTU and HOBT along with diisopropylethylamine and the reaction mixture was stirred overnight. The crude reaction mixture was purified directly by preparative HPLC on a reversed-phase C-18 column using a 0.1% trifluoroacetic acid (TFA) in acetonitrile/0.1% TFA in water gradient. Table 3 In vitro Assay of Cytotoxicity of Peptidyl Derivatives of Doxorubicin: The cytotoxicities of the non-cleaveable ohgopeptide-doxorubicin conjugates, prepared as described in Example 4, against a line of cells which is known to be killed by unmodified doxorubicin were assessed with an Alamar Blue assay. Specifically, cell cultures of LNCaP prostate tumor cells, which are a human metastatic prostate adenocarcinoma isolated from a needle biopsy of a lymph node (LNCaP.FGC: American Type Culture Collection, ATCC CRL 1740) , or DuPRO cells in 96 well plates were diluted with medium containing various concentrations of a given conjugate (final plate well volume of 200μl). The cells were incubated for 3 days at 37°C and then 20μl of Alamar Blue was added to the assay well. The cells were further incubated and the assay plates were read on a EL-310 ELISA reader at the dual wavelengths of 570 and 600 nm at 4 and 7 hours after addition of Alamar Blue. Relative percentage viability at the various concentration of conjugate tested was then calculated versus control (no conjugate) cultures. Cytotoxicities of unmodified doxorubicin and unmodified oligopeptide were also assessed. Figure 3 shows the cytotoxicity data for a representative compound (Compound 12d). EXAMPLE 6 Assessment of Enzymatically Active PSA from LNCaP Cells Enzymatic activity was demonstrated by incubating LNCaP serum free media (concentrated approximately 200 fold) with recombinant Senemogehn I protein. Approximately 0.5 μg of immunologically reactive PSA in concentrated conditioned media [determined by HYBRIDTECH (Tandem E) elisa] was mixed with approximately 3 μg of recombinant Semenogelin I and incubated for 4 hours at 37°C. At the end of the incubation, the digest mixture was analyzed by Western blot procedures. The results show that purified PSA from semen and PSA from LNCaP conditioned media generate identical proteolytic maps of the recombinant Semenogelin I protein. Thus, LNCap cells produce enzymatically active PSA. LNCaP are tumorigenic in nude mice and produce detectable levels of circulating PSA. EXAMPLE 7 Preparation of Cleavable Oligopeptide-Doxorubicin Conjugates: The derivatives of doxorubicin wherein an oligopeptide which is proteolytically cleaved by free PSA is covalently attached to the amine of the sugar moiety of the doxorubicin were prepared using the following general reaction: To a mixture of doxorubicin (Sigma) and the corresponding peptide (prepared by solid phase synthesis as described in Example 2) in DMSO was added HBTU and HOBT along with diisopropylethylamine and the reaction mixture stirred overnight. The crude reaction mixture was purified directly by preparative HPLC on a reversed-phase C-18 column using a 0.1% trifluoroacetic acid (TFA) in acetonitrile/0.1% TFA in water gradient. When reactive amine moieties were present on the peptide, such a functionahty was typically protected as the fluorenylmethyloxycarbonyl adduct, which was removed by treatment with a secondary amine, such as piperidine and the like, subsequent to conjugation with doxirubicin. The instant conjugates have a structure of the general formula and may be represented by the phrase "Ac-peptide-DOX (3')." Conjugates prepared by this method are listed in Table 5 in Figure 5. EXAMPLE 8 Assessment of the Recognition of Oligopeptide-Doxorubicin Conjugates by Free PSA : The conjugates prepared as described in Example 7 were individually dissolved in PSA digestion buffer (12 mM tris(hydroxymethyl)- aminomethane pH8.0, 25 mM NaCl, 0.5 mM CaCl2) and the solution added to PSA at a molar ration of 100 to 1. The reaction is quenched after various reaction times by the addition of trifluoroacetic acid (TFA) to a final 1% (volume/volume). The quenched reaction was analyzed by HPLC on a reversed-phase C18 column using an aqueous 0.1%TFA/acetonitrile gradient. The results of the assessment are shown in Table 5 of Figure 5. EXAMPLE 9 Assessment of the Cleavage of Oligopeptide-Doxorubicin Conjugates in Cell Conditioned Media : Cell conditioned serum-free MEMα media (phenol red minus) was collected 3 days after the addition of the media to either LNCap or Dupro (prepared as described in /. Urology, 146:915-919 (1991)) cell lines. The media was concentrated 20 fold using an Amicon® Centriprep™ concentrator with a 10,000 molecular weight cutoff. The LNCap conditioned media contained free PSA protein at, on average, approximately 100 ng/mL concentration as determined by the Tandem®- E PSA immunodetection kit (Hybritech®). There was no detectable free PSA in the Dupro cell conditioned media. 100 μL portions of concentrated conditioned media was mixed with 35 μg of a oligopeptide-doxorubicin conjugate prepared as described in Example 7 and the mixture was incubated at 37°C for 0, 4 and 24 hour time points. The reactions were stopped by the addition of ZnCl2 (to a 0.0 IM final concentration and analyzed by HPLC on a reversed-phase C18 column using an aqueous 0.1%TFA acetonitrile gradient to determine the percentage of peptide-cytotoxic agent conjugate that had been digested. The results of the assessment are shown in Table 6 of Figure 6. EXAMPLE 10 In vitro Assay of Cytotoxicity of Peptidyl Derivatives of Doxorubicin: The cytotoxicities of the cleaveable oligopeptide-doxorubicin conjugates, prepared as described in Example 7, against a line of cells which is known to be killed by unmodified doxorubicin was assessed with an Alamar Blue assay as described in Example 5. Specifically, cell cultures of LNCap prostate tumor cells or DuPRO cells in 96 well plates was diluted with medium containing various concentrations of a given conjugate (final plate well volume of 200μl). The cells were incubated for 3 days at 37°C, 20μl of Alamar Blue is added to the assay well. The cells were further incubated and the assay plates were read on a EL-310 ELISA reader at the dual wavelengths of 570 and 600 nm at 4 and 7 hours after addition of Alamar Blue. Relative percentage viabihty at the various concentration of conjugate tested was then calculated versus control (no conjugate) cultures. Cytotoxicities of the conjugates were also compared to the cytotoxicity of unmodified doxorubicin and unmodified oligopeptide assessed in the same assay. Results of this assay are shown in Table 7 of Figure 7. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: DeFeo-Jones, Deborah Feng, Dong-Mei Garsky, Victor M. Jones, Raymond E. Oliff, Allen I. (ii) TITLE OF INVENTION: NOVEL PEPTIDES (iii) NUMBER OF SEQUENCES: 146 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: DAVID A. MUTHARD (B) STREET: 126 E. Lincoln Avenue, P.O. BOX 2000 (C) CITY: RAHWAY (D) STATE: NEW JERSEY (E) COUNTRY: U.S.A. (F) ZIP: 07065 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.30 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Muthard, David A. (B) REGISTRATION NUMBER: 35,297 (C) REFERENCE/DOCKET NUMBER: 19253Y (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (908)594-3903 (B) TELEFAX: (908)594-4720 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 462 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: Met Lys Pro Asn lie lie Phe Val Leu Ser Leu Leu Leu lie Leu Glu 1 5 10 15 Lys Gin Ala Ala Val Met Gly Gin Lys Gly Gly Ser Lys Gly Arg Leu 20 25 30 Pro Ser Glu Phe Ser Gin Phe Pro His Gly Gin Lys Gly Gin His Tyr 35 40 45 Ser Gly Gin Lys Gly Lys Gin Gin Thr Glu Ser Lys Gly Ser Phe Ser 50 55 60 lie Gin Tyr Thr Tyr His Val Asp Ala Asn Asp His Asp Gin Ser Arg 65 70 75 80 Lys Ser Gin Gin Tyr Asp Leu Asn Ala Leu His Lys Thr Thr Lys Ser 85 90 95 Gin Arg His Leu G-ly Gly Ser Gin Gin Leu Leu His Asn Lys Gin Glu 100 105 110 Gly Arg Asp His Asp Lys Ser Lys Gly His Phe His Arg Val Val lie 115 120 125 His His Lys Gly Gly Lys Ala His Arg Gly Thr Gin Asn Pro Ser Gin 130 135 140 Asp Gin Gly Asn Ser Pro Ser Gly Lys Gly lie Ser Ser Gin Tyr Ser 145 150 155 160 Asn Thr Glu Glu Arg Leu Trp Val His Gly Leu Ser Lys Glu Gin Thr 165 170 175 Ser Val Ser Gly Ala Gin Lys Gly Arg Lys Gin Gly Gly Ser Gin Ser 180 185 190 Ser Tyr Val Leu Gin Thr Glu Glu Leu Val Ala Asn Lys Gin Gin Arg 195 200 205 Glu Thr Lys Asn Ser His Gin Asn Lys Gly His Tyr Gin Asn Val Val 210 215 220 Glu Val Arg Glu Glu His Ser Ser Lys Val Gin Thr Ser Leu Cys Pro 225 230 235 240 Ala His Gin Asp Lys Leu Gin His Gly Ser Lys Asp lie Phe Ser Thr 245 250 255 Gin Asp Glu Leu Leu Val Tyr Asn Lys Asn Gin His Gin Thr Lys Asn 260 265 270 Leu Asn Gin Asp Gin Gin His Gly Arg Lys Ala Asn Lys He Ser Tyr 275 280 285 Gin Ser Ser Ser Thr Glu Glu Arg Arg Leu His Tyr Gly Glu Asn Gly 290 295 300 Val Gin Lys Asp Val Ser Gin Ser Ser He Tyr Ser Gin Thr Glu Glu 305 310 315 320 Lys Ala Gin Gly Lys Ser Gin Lys Gin He Thr He Pro Ser Gin Glu 325 330 335 Gin Glu His Ser Gin Lys Ala Asn Lys He Ser Tyr Gin Ser Ser Ser 340 345 350 Thr Glu Glu Arg Arg Leu His Tyr Gly Glu Asn Gly Val Gin Lys Asp 355 360 365 Val Ser Gin Arg Ser He Tyr Ser Gin Thr Glu Lys Leu Val Ala Gly 370 375 380 Lys Ser Gin He Gin Ala Pro Asn Pro Lys Gin Glu Pro Trp His Gly 385 390 395 400 Glu Asn Ala Lys Gly Glu Ser Gly Gin Ser Thr Asn Arg Glu Gin Asp 405 410 415 Leu Leu Ser His Glu Gin Lys Gly Arg His Gin His Gly Ser His Gly 420 425 430 Gly Leu Asp He Val He He Glu Gin Glu Asp Asp Ser Asp Arg His 435 440 445 Leu Ala Gin His Leu Asn Asn Asp Arg Asn Pro Leu Phe Thr 450 455 460 (2) INFORMATION FOR SEQ ID Nθ:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2 : Gly Lys Gly He Ser Ser Gin Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:3 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID Nθ:3: Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4 : Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Arg Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:5 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Ser Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 25 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: Gly Arg Lys Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu Glu 1 5 10 15 Arg Arg Leu His Tyr Gly Glu Asn Gly 20 25 (2) INFORMATION FOR SEQ ID Nθ:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7 : Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:9 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9 : Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: Asn Lys He Ser Tyr Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: Ala Ser Ala Gly Thr Pro Gly Ala 1 5 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13 Asn Lys He Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: Lys He Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 12 (D) OTHER INFORMATION: /note= "any natural amino acid" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Xaa Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: Asn Lys He Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: Asn Lys He Ser Tyr Gin Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: Ala Asn Lys He Ser Tyr Gin Ser Ser Ser 1 5 10 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: Gin Leu Asp Asn Lys He Ser Tyr Gin Ser Ser Ser Thr His Gin Ser 1 5 10 15 Ser (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: Asn Arg He Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: Asn Lys Val Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: Asn Lys Met Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: Asn Lys Leu Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: Asn Lys He Thr Tyr Gin Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: Asn Lys He Ser Phe Gin Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: Asn Lys He Ser Trp Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: Asn Lys He Ser Tyr Asn Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: Asn Lys He Ser Tyr Gin Thr Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Asn Lys He Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: Gin Lys He Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: Asn Arg He Thr Tyr Gin Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: Asn Arg He Ser Phe Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: Gin Lys He Ser Tyr Gin Thr Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:35 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: Asn Arg He Ser Trp Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36 : Asn Arg He Ser Tyr Gin Thr Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: Asn Lys He Thr Tyr Gin Thr Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal ( i) SEQUENCE DESCRIPTION: SEQ ID NO:38: Asn Lys Leu Ser Tyr Gin Thr Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: Gin Lys Leu Ser Tyr Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL:* NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: Asn Arg Leu Ser Tyr Gin Thr Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE,DESCRIPTION: SEQ ID NO:41: Asn Lys Val Ser Phe Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: Asn Arg Val Ser Trp Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: Gin Lys Val Ser Tyr Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: Asn Lys He Ser Tyr Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:45: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: Gly Glu Gin Gly Val Gin Lys Asp Val Ser Gin Ser Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:46: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide [iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: Gly Lys Gly He Ser Ser Gin Tyr Ser Asn Thr Asp Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: Gly Glu Asn Gly Leu Gin Lys Asp Val Ser Gin Ser Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: Gly Glu Asn Gly Val Asn Lys Asp Val Ser Gin Ser Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: Gly Glu Asn Gly Val Gin Arg Asp Val Ser Gin Arg Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Lys Ser He Tyr Ser 1 5 10 15 Gin Thr Glu [2) INFORMATION FOR SEQ ID NO:51: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: Gly Glu Asn Gly Val Gin Lys Asp Leu Ser Gin Thr Ser He Tyr Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Ser Ser He Phe Ser 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:53: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: Gly Glu Asn Gly Val Gin Lys Asp Met Ser Gin Ser Ser He Tyr Thr 1 5 10 15 Gin Thr Glu (2) INFORMATION FOR SEQ ID NO:54: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Arg Ser He Tyr Thr 1 5 10 15 Gin Thr Glu [2) INFORMATION FOR SEQ ID NO:55: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Ser Ser He Tyr Ser 1 5 10 15 Gin Ser Glu (2) INFORMATION FOR SEQ ID NO:56: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: Gly Glu Asn Gly Val Gin Lys Asp Val Ser Gin Arg Ser He Tyr Ser 1 5 10 15 Asn Thr Glu (2) INFORMATION FOR SEQ ID NO:57: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57: Gly Lys Ala He Ser Ser Gin Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:58: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58: Gly Lys Gly He Ser Ser Gin Tyr Ser Asn Ser Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:59: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59: Gly Arg Gly He Ser Ser Gin Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:60: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60: Gly Lys Gly He Thr Ser Gin Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:61: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 61: Gly Lys Gly He Ser Thr Gin Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:62: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL:■ NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: Gly Lys Gly He Ser Ser Asn Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:63: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63: Ala Lys Gly He Ser Ser Gin Tyr Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:64: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: Gly Lys Gly He Ser Ser Gin Phe Ser Asn Thr Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:65: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65: Gly Lys Gly He Ser Ser Gin Tyr Thr Asn Ser Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:66: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 66: Gly Lys Gly He Ser Ser Gin Tyr Ser Asn Ser Glu Glu Arg Leu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:67: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 25 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 67 : Ser Gin Lys Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu Glu 1 5 10 15 Arg Arg Leu His Tyr Gly Glu Asn Gly 20 25 (2) INFORMATION FOR SEQ ID NO:68: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide [iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68: He Ser Tyr Gin Ser Ser Ser Thr 1 5 (2) INFORMATION FOR SEQ ID NO:69: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69: Ala Asn Lys He Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:70: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70: Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Leu 1 5 10 (2) INFORMATION FOR SEQ ID NO:71: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71: Ala Asn Gly He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:72: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72: Ala Asn Pro He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:73: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73: Ala Asn Lys He Ser Tyr Gin Ser Ala Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:74: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74: Ala Asn Lys He Ser Tyr Gin Ser Ser Lys Thr Glu 1 ' 5- 10 (2) INFORMATION FOR SEQ ID NO:75: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75: Ala Asn Lys He Ser Tyr Gin Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:76: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 5 (D) OTHER INFORMATION: /label= d-serine /note= "unnatural configuration of the amino acid" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76: Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:77: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 4 (D) OTHER INFORMATION: /label= d-isoleucine /note= "unnatural amino acid stereochemical configuration 1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77: Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:78: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78: Ala Asn Lys He Ser Tyr Gin Ser Ser Gin Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:79: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO.-79: Ala Asn Lys He Ser Tyr Gin Ser Ala Lys Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:80: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 3 (D) OTHER INFORMATION: /label= d-lysine /note= "unnatural amino acid stereochemical configuration" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:80: Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:81: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO ( iv) ANTI-SENSE : NO (v) FRAGMENT TYPE : internal (xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 81 : Ala Asn Lys He Ser Tyr Gin Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:82: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82: Ala Asn Lys Ser Tyr Gin Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:83: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83: Ala Asn Lys He Tyr Gin Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:84: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84: Ala Asn Lys Ala Ser Tyr Gin Ser Ala Ser Thr Glu 1 5 10 [2) INFORMATION FOR SEQ ID NO:85: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85: Ala Asn Glu He Ser Tyr Gin Ser Ala Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:86: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86: Lys He Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:87: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87: Ser Tyr Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:88: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88: Ser Tyr Gin Ser Ser Thr Leu 1 5 (2) INFORMATION FOR SEQ ID NO:89: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89: Ala Ser Tyr Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:90: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90: Glu He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:91: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91: Ala Asn Glu He Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:92: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92: Ala Asn Lys He Ser Tyr Tyr Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:93: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93: Ala Asn Lys He Ser Tyr Tyr Ser Ala Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:94: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94: Ala Ser Tyr Gin Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:95: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95: Ala Asn Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:96: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96: Ala Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:97: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97: Ser Tyr Gin Ser Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:98: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98: Ala Asn Lys Ala Ser Tyr Gin Ser Ala Ser Cys 1 5 10 (2) INFORMATION FOR SEQ ID NO:99: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99: Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:100: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 100: Tyr Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO: 101: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101: Ser Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:102: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102: Ala Asn Lys He Ser Gin Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:103: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 3 (D) OTHER INFORMATION: /label= unnatural /note= "ornithine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103: Ala Asn Xaa He Ser Tyr Gin Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:104: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal ( ix) FEATURE : (A) NAME/KEY: Peptide (B) LOCATION: 2 (D) OTHER INFORMATION: /label= unnatural /note= "3, 4-dichlorophenalanine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104: Ser Xaa Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:105: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 2 (D) OTHER INFORMATION: /label= unnatural /note= " (3-pyridinyl)alanine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:105: Ser Xaa Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:106: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:106: Ser Lys Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:107: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107: Ser Tyr Gin Ser Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:108: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: /label= unnatural /note= "epsilon aminocaproic acid" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:108: Xaa Tyr Gin Ser Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:109: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 4 (D) OTHER INFORMATION: /label= unnatural /note= "N-methylisoleucine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109: Ala Asn Lys Xaa Ser Tyr Gin Ser Ser Thr Glu 1 5 10 (2) INFORMATION FOR SEQ ID NO:110: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:110: Ser Tyr Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:111: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111: Tyr Gin Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:112: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:112: Ser Tyr Lys Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:113: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide [iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113: Ser Tyr Tyr Ser Ser Thr Glu 1 5 (2) INFORMATION FOR SEQ ID NO:114: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114: Ser Tyr Gin Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:115: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115: Ser Tyr Gin Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:116: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: /label= unnatural /note= "2, 3-diaminopropionic acid" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116: Xaa Tyr Gin Ser Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:117: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE : internal (xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 117 : Ala Asn Lys He Ser Tyr Gin Ser Ser Ser Thr 1 5 10 (2) INFORMATION FOR SEQ ID NO:118: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:118: Ala Asn Lys Ala Ser Tyr Gin Ser Ala Ser Thr Leu 1 5 10 (2) INFORMATION FOR SEQ ID NO:119: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:119: Ala Asn Lys Ala Ser Tyr Gin Ser Ala Ser Leu 1 5 10 (2) INFORMATION FOR SEQ ID NO:120: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120: Ala Asn Lys Ala Ser Tyr Gin Ser Ser Ser Leu 1 5 10 (2) INFORMATION FOR SEQ ID NO:121: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 121: Ala Asn Lys Ala Ser Tyr Gin Ser Ser Leu 1 5 10 (2) INFORMATION FOR SEQ ID NO:122: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 7 (D) OTHER INFORMATION: /label= d-leucine /note= "unnatural amino acid stereochemical configuration" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122: Ser Tyr Gin Ser Ser Thr Leu 1 5 (2) INFORMATION FOR SEQ ID NO:123: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:123: Ala Asn Lys Ala Ser Tyr Ala Ser Ser Ser Leu 1 5 10 (2) INFORMATION FOR SEQ ID NO:124: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:124: Lys Tyr Gin Ser Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:125: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:125: Ser Tyr Gin Ser Ser Lys Leu 1 5 (2) INFORMATION FOR SEQ ID NO:126: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 7 (D) OTHER INFORMATION: /label* * -, d-leucine /note= "unnatural amino acid stereochemical configuration" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126: Ser Tyr Gin Ser Ser Lys Leu 1 5 (2) INFORMATION FOR SEQ ID NO:127: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127: Asn Lys He Ser Tyr Tyr Ser 1 5 (2) INFORMATION FOR SEQ ID NO:128: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128: Asn Lys Ala Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO:129: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129: Ser Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:130: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130: Asn Lys He Ser Tyr Gin Ser Ala 1 5 (2) INFORMATION FOR SEQ ID NO:131: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 131: Ala Asn Lys He Ser Tyr Tyr Ser 1 5 (2) INFORMATION FOR SEQ ID NO: 132: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132: Ala Asn Lys Ala Ser Tyr Gin Ser 1 5 (2) INFORMATION FOR SEQ ID NO:133: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:133: Ser Tyr Gin Ser Ser Thr 1 5 (2) INFORMATION FOR SEQ ID NO:134: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:134: Ser Tyr Gin Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO: 135: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135: Ser Tyr Gin Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:136: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136: Ala Asn Lys He Ser Tyr Gin Ser Ala 1 5 (2) INFORMATION FOR SEQ ID NO:137: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:137: Ala Asn Lys He Ser Tyr Tyr Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:138: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:138: Ala Asn Lys He Ser Tyr Tyr Ser Ala 1 5 (2) INFORMATION FOR SEQ ID NO:139: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:139: Ala Asn Lys Ala Ser Tyr Gin Ser Ala 1 5 (2) INFORMATION FOR SEQ ID NO:140: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:140: Lys Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:141: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal [ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: /label= homoarginine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141: Xaa Tyr Gin Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:142: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:142: Lys Tyr Gin Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:143: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal [ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: /label= homoarginine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:143: Xaa Tyr Gin Ser Ser Ser 1 5 (2) INFORMATION FOR SEQ ID NO:144: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:144: Ser Tyr Gin Ser Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:145: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: /label= homoarginine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:145: Xaa Tyr Gin Ser Ser Ser Leu 1 5 (2) INFORMATION FOR SEQ ID NO:146: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (v) FRAGMENT TYPE: internal (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 7 (D) OTHER INFORMATION: /label= norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:146: Lys Tyr Gin Ser Ser Ser Leu 1 5

Claims: WHAT IS CLAIMED IS: 1. An oligopeptide that comprises a sequence of amino acids that is recognized and selectively proteolytically cleaved by free prostate specific antigen. 2. The oligopeptide according to Claim 1 wherein the sequence of amino acids is a) AsnLysIleSerTyrGln|Ser (SEQ.ID.NO.: 13), b) LysIleSerTyrGln|Ser (SEQ.ID.NO.: 14), c) GlyGluAsnGlyValGlnLysAspValSerGlnXaaSerIleTyr|SerGlnThrGlu (SEQ.ID.NO.: 15) , d) GlyLysGlyIleSerSerGlnTyr|SerAsnThrGluGluArgLeu (SEQ.ID.NO.: 2), e) AsnLysIleSerTyrTyr|Ser (SEQ.ID.NO.: 127), f) AsnLysAlaSerTyrGln|Ser (SEQ.ID.NO.: 128), g) SerTyrGln|SerSer (SEQ.ID.NO.: 129); h) LysTyrGln|SerSer (SEQ.ID.NO.: 140); or i) hArgTyrGln|SerSer (SEQ.ID.NO.: 141); wherein hArg is homoarginine and Xaa is any natural amino acid. 3. The oligopeptide according to Claim 2 wherein the sequence of amino acids is a) AsnLysIleSerTyrGln|SerSer (SEQ.ID.NO.: 16), b) Asr_LysIleSerTyrGln|SerAla (SEQ.ID.NO.: 130), c) AsnLysIleSerTyrGln|SerSerSer (SEQ.ID.NO.: 17), d) AlaAsnLysIleSerTyrGln|SerSerSer (SEQ.ID.NO.: 18), e) LysIleSerTyrGln|SerSerSerThrGlu (SEQ.ID.NO.: 19), f) GlyGluAsnGlyValGlnLysAspValSe _lr rgSerIleTyr|SerGlnThrGlu (SEQ.ID.NO.: 4), g) GlyGluAsnGlyValGlnLysAspValSerGlnSerSerIleTyr|SerGbThrGlu (SEQ.ID.NO.: 5), h) AlaAsnLysIleSerTyrTyr|Ser (SEQ.ID.NO.: 131), i) AlaAsnLysAlaSerTyrGln|Ser (SEQ.ID.NO.: 132), j) SerTyrGln|SerSerThr (SEQ.ID.NO.: 133), k) SerTyrGln|SerSerSer (SEQ.ID.NO.: 134), 1) LysTyrGln|SerSerSer (SEQ.ID.NO.: 142), m) hArgTyrGln|SerSerSer (SEQ.ID.NO.: 143), or n) SerTyrGln|SerSerLeu (SEQ.ID.NO.: 135). 4. The oligopeptide according to Claim 2 wherein the amino acid sequence is a) AsnLysIleSerTyrGln |SerSerSerThr (SEQ.ID.NO.: 10), b) AlaAsnLysIleSerTyrGln|SerAla (SEQ.ID.NO.: 136), c) AsnLysIleSerTyrGln|SerSerSerThrGlu (SEQ.ID.NO.:3 ), d) AlaAsnLysIleSerTyrGln|SerSerSerThrGlu (SEQ.ID.NO.: 11), e) GlyGluAsnGlyValGlriysAspValSerGlnArgSerIleTyr|SerGlnThrGlu (SEQ.ID.NO.: 4), f) AlaAsnLysIleSerTyrTyr|SerSer (SEQ.ID.NO.: 137), g) AlaAsr_LysIleSerTyrTyr|SerAla (SEQ.ID.NO.: 138), h) AlaAsnLysAlaSerTyrGln|SerAla (SEQ.ID.NO.: 139), or i) AlaSerTyrGln|SerSerLeu (SEQ.ID.NO.: 94). 5. The oligopeptide according to Claim 2 wherein the amino acid sequence is a) GlyArgLysAlaAsnLysIleSerTyrGm|SerSerSerThrGluGluArgArg LeuHisTyr GlyGluAsnGly (SEQ.ID.NO.: 6). 6. The oligopeptide according to Claim 1 which is selected from: AsnArgIleSerTyrGln|Ser (SEQ.ID.NO.: 21 ), AsnLysValSerTyrGln|Ser (SEQ.ID.NO.: 22), AsnLysMetSerTyrGln|SerSer (SEQ.ID.NO.: 23), AsnLysLeuSerTyrGln|SerSer (SEQ.ID.NO.: 24), AsnLysIleThrTyrGln|SerSerSer (SEQ.ID.NO.: 25), AsnLysIleSerPheGln|SerSerSer (SEQ.ID.NO.: 26), AsnLysIleSerT Gln|SerSerSerThr (SEQ.ID.NO.: 27), AsnLysIleSerTyrAsn|SerSerSerThr (SEQ.ID.NO.: 28), AsnLysIleSerTyrGln|ThrSerSerThr (SEQ.ID.NO.: 29), AsnLysIleSerTyrGln|Ser (SEQ.ID.NO.: 30), GlnLysIleSerTyrGln|SerSer (SEQ.ID.NO.: 31), AsnArgIleThrTyrGln|SerSerSer (SEQ.ID.NO.: 32), AsnArgIleSerPheGln|SerSerSerThr (SEQ.ID.NO.: 33), AsnArgIleSerTφGln|SerSerSerThr (SEQ.ID.NO.: 35), AsnArgIleSerTyrGln|ThrSerSerThr (SEQ.ID.NO.: 36), AsnLysIleThfTyrGln|ThrSerSerThr (SEQ.ID.NO.: 37), AsnLysLeuSerTyrGm|ThrSerSerThr (SEQ.ID.NO.: 38), GlnLysLeuSerTyrGln|SerSerSerThr (SEQ.ID.NO.: 39), AsnArgLeuSerTyrGln|ThrSerSerThr (SEQ.ID.NO.: 40), AsnLysValSerPheGln|SerSerSerThr (SEQ.ID.NO.: 41), AsnArgValSerTφGln|SerSerSerThr (SEQ.ID.NO.: 42), GlnLysValSerTyrGln|SerSerSerThr (SEQ.ID.NO.: 43), GlnLysIleSerTyrGln|ThrSerSerThr (SEQ.ID.NO.: 34), or AsnLysIleSerTyrGln|SerSerSerThr (SEQ.ID.NO.: 44). 7. The oligopeptide according to Claim 1 which is AlaAsnLysIleSerTyrGln|SerSerSerThrGlu-amide (SEQ.ID.NO. : 11 ) Ac-AlaAsnLysIleSerTyrGln|SerSerSerThrLeu (SEQ.ID.NO.: 70) Ac-AlaAsnLysIleSerTyrGln|SerSerSerThrGlu-amide (SEQ.ID.NO.: 11) Ac-AlaAsnLysIleSerTyrGln|SerSerSerThrLeu-amide (SEQ.ID.NO.: 70) Ac-AlaAsnLysIleSerTyrGln|SerAlaSerThrGlu-amide (SEQ.ID.NO.: 73) Ac-AlaAsnLysIleSerTyrGln|SerSerLysThrGlu-amide (SEQ.ID.NO.: 74) Ac-AlaAsnLysIleSerTyrGln|SerSerThrGlu-amide (SEQ.ID.NO.: 75) Ac-AlaAsnLysIleSerTyrGm|SerSerGlnThrGlu-amide (SEQ.ID.NO.: 78) Ac-AlaAsnLysIleSerTyrGln|SerAlaLysThrGlu-amide (SEQ.ID.NO. :79) Ac-AlaAsnLysIleSerTyrGln|SerThrGlu-amide (SEQ.ID.NO.: 81) Ac-AlaAsnLysSerTyrGln|SerSerThrGlu-amide (SEQ.ID.NO.: 82) Ac-AlaAsnLysAlaSerTyrGln|SerAlaSerThrGlu-amide (SEQ.ID.NO.: 84) Ac-AlaAsnGluIleSerTyrGlnlSerAlaSerThrGlu-amide (SEQ.ID.NO.: 85) Ac-AsnLysIleSerTyιGln[SerSer-amide (SEQ.ID.NO.: 16) Ac-LysIleSerTyrGln|SerSer-amide (SEQ.ID.NO.: 86) Ac-SerTyrGln|SerSerThrGlu-amide (SEQ.ID.NO.: 87) Ac-AlaSerTyrGln|SerSerThrGlu-amide (SEQ.ID.NO.: 89) Ac-AlaAsnLysIleSerTyrTyr|SerSerSerThrGlu-amide (SEQ.ID.NO.: 92) Ac-AlaAsnLysIleSerTyrTyr|SerAlaSerThrGlu-amide (SEQ.ID.NO.: 93) Ac-AlaSerTyrGln|SerSerLeu-amide (SEQ.ID.NO.: 94) Ac-AlaAsnSerTyrGln|SerSerSerThrGlu-amide (SEQ.ID.NO.: 95) Ac-AlaSerTyrGln|SerSerSerThrGlu-amide (SEQ.ID.NO.: 96) Ac-SerTyrGln|SerSerSerThrGlu-amide (SEQ.ID.NO.: 97) or Ac-AlaAsnLysAlaSerTyrGln|SerAlaSerCys-amide (SEQ.ID.NO.: 98). 8. An assay for determining proteolytic activity of free prostate specific antigen in a sample, comprising the steps of: (a), reacting a substrate, wherein the substrate is an oligopeptide that comprises a sequence of amino acids that is recognized and selectively proteolytically cleaved by free prostate specific antigen, with the sample; and (b), detecting whether the substrate has been cleaved. 9. The assay according to Claim 8 wherein the step of detecting whether the substrate has been cleaved comprises analyzing the assay mixture by high performance liquid chromatography. 10. An assay for identifying compounds which inhibit the proteolytic activity of prostate specific antigen, comprising: (a), reacting a substrate, wherein the substrate comprises a sequence of amino acids that is recognized and selectively proteolytically cleaved by free prostate specific antigen, with free prostate specific antigen in the presence of a test substance; and (b), detecting whether the substrate has been cleaved, in which the ability of the test substance to inhibit proteolytic activity of prostate specific antigen is indicated by a decrease in the cleavage of the substrate as compared to the cleavage of the substrate in the absence of the test substance. 11. The assay according to Claim 10 wherein the step of detecting whether the substrate has been cleaved comprises analyzing the assay mixture by high performance liquid chromatography. 12. A conjugate which is useful for the treatment of prostate cancer which comprises a cytotoxic agent attached to a oligopeptide, wherein the oligopeptide comprises a sequence of amino acids that is recognized and selectively proteolytically cleaved by free prostate specific antigen, wherein the means of attachment is a covalent bond or a chemical hnker. 13. The conjugate according to Claim 12 wherein the cytotoxic agent is a member of a class of cytotoxic agents selected from the following classes: a) anthracycline family of drugs, b) the vinca alkaloid drugs, c) the mitomycins, d) the bleomycins, e) the cytotoxic nucleosides, f) the pteridine family of drugs, g) diynenes, h) estramustine, i) cyclophosphamide, and h) the podophyllotoxins. 14. The conjugate according to Claim 12 wherein the cytotoxic agent is selected from the following cytotoxic agents: a) doxorubicin, b) carminomycin, c) daunorubicin, d) aminopterin, e) methotrexate, f) methopterin, g) dichloro-methotrexate, 0 h) mitomycin C, i) porfiromycin, j) 5-fluorouracil, k) 6-mercaptopurine, 1) cytosine arabinoside, 5 m) podophyllotoxin, n) etoposide, o) etoposide phosphate, p) melphalan, q) vinblastine, 0 r) vincristine, s) leurosidine, t) vindesine, u) estramustine, v) cisplatin, 5 w) cyclophosphamide, and x) leurosine. 15. The conjugate according to Claim 12 wherein the cytotoxic agent is selected from doxorubicin and vinblastine or a ° cytotoxic derivative thereof. 16. The conjugate according to Claim 12 wherein the cytotoxic agent is doxorubicin or a cytotoxic derivative thereof. 17. The conjugate according to Claim 16 of the formula I: R wherein: oligopeptide is an oligopeptide which is specifically recognized by the free prostate specific antigen (PSA) and is capable of being proteolytically cleaved by the enzymatic activity of the free prostate specific antigen; XL is absent or is an amino acid selected from: a) phenylalanine, b) leucine, c) valine, d) isoleucine, e) (2-naphthyl)alanine, f) cyclohexylalanine, g) diphenylalanine, h) norvaline, and j) norleucine; R is hydrogen or -(C=0)Rl; and R 1 is Cl-C6-alkyl or aryl. 18. The conjugate according to Claim 17 wherein: oligopeptide is an oligomer that comprises an amino acid sequence selected from: a) AsnLysIleSerTyrGln|Ser (SEQ.ID.NO.: 13), b) LysIleSerTyrGln|Ser (SEQ.ID.NO.: 14), c) GlyGluAsnGlyValGlιιLysAspValSerGlnXaaSerIleTyr|SerGlnThrGlu (SEQ.ID.NO.: 15) , d) GlyLysGlyIleSerSerGlnTyr|SerAsnThrGluGluArgLeu (SEQ.ID.NO.: 2), e) AsnLysIleSerTyrTyr|Ser (SEQ.ID.NO.: 127), f) AsnLysAlaSerTyrGln|Ser (SEQ.ID.NO.: 128), g) SerTyrGln|SerSer (SEQ.ID.NO.: 129), and h) hArgTyrGln|SerSer (SEQ.ID.NO.: 141); wherein hArg is homoarginine and Xaa is any natural amino acid; XL is absent or is an amino acid selected from: a)leucine, b) isoleucine, and d) valine; and R is acetyl, pivaloyl or benzoyl. 19. The conjugate according to Claim 16 which is selected from: wherein X is: , O II AcHN — AlaAsnLyslleSerTyrGlnSerSerSerThr-C- (SEQ.ID.NO.: 117), O II AcHN — AlaAsnLyslleSerTyrGlnSerSerSerThrLeii-C- (SEQ.ID.NO.: 70), O II AcHN — AlaAsnLysAlaSerTyrGlnSerAlaSerThrLeu-C- (SEQ.ID.NO.: 118), O I I AcHN — AlaAsnLysAlaSerTyrGlnSerAlaSerLeu-C- (SEQ.ID.NO.: 119), AcHN — AlaAsnLysAlaSerTyrGlnSerSerSerLeu-C- (SEQ.ID.NO.: 120), O II AcHN — AlaAsnl_ysAlaSerTyrGlnSerSerl_eu-C- (SEQ.ID.NO.: 121 ), O II AcHN — SerTyrGlnSerSerSerLeu-C- (SEQ.ID.NO.: 144), O II AcHN — hArgTyrG!nSerSerSeιteu-C- (SEQ.ID.NO.: 145), O II AcHN — LysTyrGlnSerSerSerLeu-C- (SEQ.ID.NO.: 124), or O ll AcHN — LysTyrGlnSerSerNle -C- (SEQ.ID.NO.: 146). 20. The conjugate according to Claim 15 of the formula II: - NH 2 wherein: oligopeptide is an oligopeptide which is specifically recognized by the free prostate specific antigen (PSA) and is capable of being proteolytically cleaved by the enzymatic activity of the free prostate specific antigen.

Inventors: DEFEO-JONES DEBORAH, FENG DONG-MEI, GARSKY VICTOR M, JONES RAYMOND E, OLIFF ALLEN I, DEFEO-JONES, DEBORAH, FENG, DONG-MEI, GARSKY, VICTOR, M., JONES, RAYMOND, E., OLIFF, ALLEN, I.
Applicants: DEFEO-JONES DEBORAH, FENG DONG-MEI, GARSKY VICTOR M, JONES RAYMOND E, MERCK & CO INC, OLIFF ALLEN I, DEFEO-JONES, DEBORAH, FENG, DONG-MEI, GARSKY, VICTOR, M., JONES, RAYMOND, E., MERCK & CO., INC., OLIFF, ALLEN, I.
Application year: 1995
Main classification: A61K38
IPC codes: A61K31, A61K38, A61K47, A61P13, A61P35, A61P43, C07H15, C07K7, C07K14, C07K17, C12Q1, G01N33