PEPTIDES AND COMPOUNDS THAT BIND TO THE IL-1 RECEPTOR

Abstract: Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of: (1) WXXXGZ1W; (2) XXQZ5YZ6XX and (3) Z23NZ24SZ25Z26Z27Z28Z29Z30L. Also provided are peptides which bind to the IL-1RtI, which are 11 to 40 amino acids in length, which comprise the core sequence of amino acids Z31XZ41Z32Z34Z36Z42Z37Z38.

Description: PEPTIDES AND COMPOUNDS THAT BIND TO THE IL-1 RECEPTOR BACKGROUND OF THE INVENTION The present invention provides peptides and compounds that bind the interleu in 1 receptor (IL-IR) , methods for assaying interleukin 1 (IL-1) , and methods for inhibiting the binding of IL-1 to the IL-IR. The invention has application in the fields of biochemistry and medicinal chemistry and particularly provides IL-1 antagonists for use in the treatment of human disease. IL-1 is a polypeptide hormone, a cytokine, that exists in various forms, the genes for two of which, IL-lα and IL-1/3, have been cloned. Unless otherwise noted, "IL-1" refers to either or both IL-lα and IL-1/3. These two genes are both located in chromosome 2; each gene contains 7 exons, and the two genes are homologous in a region of the sixth exon. Both IL-lα and IL-lβ initially exist as 31 kD precursors but are processed by proteases to produce the amino terminus of the 17.5 kD mature proteins. Receptors for IL-1 recognize the α and β forms, and both forms have similar biological properties. See Dinarello (1991) Blood 77 (8) : 1627-1652, incorporated herein by reference. The biological properties of IL-1 include mediating many immunological and inflammatory responses to infection and tissue injury. Because of the role of IL-1 in these important processes, the therapeutic benefits of IL-1 and derivatives of IL-1 have been extensively studied. See U.S. Patent Nos. 5,075,288 and 5,077,219, incorporated herein by reference. Inappropriate production or response to IL-1 plays a role in many chronic inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, psoriasis, inflammatory bowel disease, encephalitis, glomerulonephritis, and respiratory distress syndrome. See Bender and Lee (1989) Ann. Rep . Med . Chem . 25:185-193; and U.S. Patent No. 5,075,222, particularly columns 1 to 3, each of which is incorporated herein by reference. Because of the important biological properties of IL-1, IL-1 inhibitors have been extensively studied, as reviewed in Larrick (1989) Immunol . Today 10 (2) :61-66, incorporated herein by reference. IL-1 inhibitors include the naturally occurring IL-lra protein and soluble IL-1 receptor, as well as derivatives of IL-lα and IL-1/3 produced by recombinant DNA technology, as discussed in Dinarello, supra . See also PCT patent publication Nos. 91/08285, published June 13, 1991, and 91/02127, published November 14, 1991, incorporated herein by reference. In similar fashion, scientists have studied the IL-IR, as reviewed in Dower and Urdal (1987) Immunol . Today 8(2):46-51, incorporated herein by reference. Two distinct naturally occurring types of the IL-IR are known to exist, and the corresponding genes have been cloned and expressed, as reported in Dower et al . , (1990) J . Clin . Immunol . 10 (6) :289-299; PCT patent publication No. 91/00742; U.S. Patent No. 4,968,607, and McMahon et al . , (1991) EMBO J . 10(10) :2821-2832, each of which is incorporated herein by reference. The type I receptor (IL-lRtI) is 80 kD in size, while the type II receptor (IL-lRtll) is 60 kD in size. A number of studies regarding whether IL-lRtI and IL-lRtll have different affinities for ligands have been conducted; see Slack et al . (1993) J . Biol . Chem . 268:2513-2524 and Hannum et al . , (1990) Nature 343:336-340. The availability of cloned genes for IL-lRtI and ILlRtll, including a soluble IL-lRtI derivative, facilitates the search for agonists and antagonists of these important receptors. The availability of the recombinant receptor protein allows the study of receptor-ligand interaction in a variety of random and semi-random peptide diversity generation systems. These systems include the "peptides on plasmids" system described in U.S. Patent No. 5,270,170, the "peptides on phage" system described in U.S. patent application Serial No. 718,577, filed June 20, 1991, and in Cwirla et al . , (1990) Proc . Natl . Acad . Sci . USA 87:6378-6382, and the "very large scale immobilized polymer synthesis" system described in U.S. Patent No. 5,143,854; PCT patent publication No. 90/15070, published December 13, 1990; U.S. patent application Serial No. 624,120, filed December 6, 1990; Fodor et al., February 15, 1991, Science 251:767-773; Dower and Fodor (1991) Ann . Rep . Med . Chem . 26 :271-180; and U.S. patent application Serial No. 805,727, filed December 6, 1991; each of the foregoing patent applications and publications is incorporated herein by reference. There remains a need, however, for compounds that bind to or otherwise interact with the IL-IR, both for studies of the important biological activities mediated by this receptor and for treatment of disease. The present invention provides such compounds. SUMMARY OF THE INVENTION In one embodiment, the invention provides compounds that bind to IL-lRtI. These compounds generally comprise a molecular weight less than about 3000 Daltons, a binding affinity to an interleukin type I receptor as expressed by an IC50 standard of no more than about 2.5 mM. Further, the binding of the compound to the IL-1 receptor is competitively inhibited by a second compound having from seven to forty amino acids in length, which comprises a core sequence of amino acids XXQZ 5 YZ 6 XX where X can be selected from any one of the 20 genetically coded L-amino acids; Z 5 is P or Aze where Aze is azetidine; and Z 6 is S, A, V, or L; or a sequence of amino acids WXXXGZ-LW where each amino acid is indicated by standard one letter abbreviation; each X can be selected from any one of the 20 genetically coded L-amino acids; and Z x is L, I, A, or Q. In an alternative embodiment, the binding of the compound to the IL-1 type I receptor is competitively inhibited by a compound of 11 to 40 amino acids in length that binds to the interleukin-1 type I receptor and comprises a core sequence of amino acids 23 24 39 25 26 27 28 29 30 40' Where Z 3 I S D or Y; ^2Λ ^"^ ' or T ; Z 39 is S , T or A ; Z 25 is S or ; Z 26 is s or γ ; z 27 ^ s D ' Q, E or V; Z 28 is N, S, K, H or ; Z 29 is F or L; Z 30 is D, N, S or L; and Z 40 is L, I, Q, M or A. In a further embodiment, peptides are seven to forty or more amino acid residues in length, preferably seven to twenty-five amino acid residues in length, and comprise a core sequence of amino acids WXXXGZ- j W where each amino acid is indicated by the standard one letter abbreviation; each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids; and Z x is L, I, A, or Q. More preferably, the core sequence of amino acids will comprise WZ^XGZ i W where X can be selected from any one of the 20 genetically coded L-amino acids; Z 2 is L, I, A, or Q; and Z 2 is D, G, N, S, or T. In a more preferred embodiment, the core sequence of amino acids will comprise WZ 2 Z 3 Z 4 GZ where Z χ is L, I, A, or Q; Z 2 is D, G, N, S, or T; Z 3 , is D, E, H, M, N, Q, R, S, T, or V; and Z 4 is A, D, F, H, K, N, Q, R, T, or Y. Most preferably, the core sequence of amino acids comprise Z 2 Z 3 Z 4 GZ 1 where Z λ is L or I; Z 2 is D, S, or T; Z 3 is D, E, or T; and Z 4 is D, H, N, R, or T. An especially preferred embodiment is one having the substitution patterns just described, but comprising 8, 10, or 12 amino acid residues. An especially preferred peptide has the sequence S DTRGL VE. According to another embodiment, the peptides are eight to forty or more amino acid residues in length, preferably eight to twenty-five amino acid residues in length, and comprise a core sequence of amino acids XXQZ 5 YZ 6 XX where X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids or unnatural amino acids; Z 5 is P or Aze where Aze (or J) is azetidine; and Z 6 is S, A, V, or L. More preferably, the sequence of amino acids will comprise Z 7 XQZ 5 YZ 6 XX where X can be selected from any one of the 20 genetically coded L-amino acids; Z 5 is P or J; Z 6 is S, A, V, or L; and Z 7 is Y, , or F. In a more preferred embodiment, the core sequence of amino acids will comprise Z 7 Z 8 QZ 5 YZ 6 Z g Z 10 where Z 5 is P or Aze where Aze is azetidine; Z 6 is S, A, V, or L; Z 7 is Y, W, or F; Z 8 is E, F, V, W, or Y; Z 9 is M, F, V, R, Q, K, T, S, D, L, I, or E; and Z 10 is E, L, , V, H, I, G, A, D, L, Y, N, Q or P. More preferably, Z 9 is V, L, I, or E; and Z 10 is Q or P. Most preferably, the core peptide will comprise a sequence of amino acids Z 11 Z 7 Z 8 QZ 5 YZ 6 Z 9 Z 10 , where Z 8 is Y, or F; and Z χι is V, L, I, E, P, G, Y, M, T, or, D. Preferred peptides include FEWTPGY QPYALPL, FEWTPGYWQJYALPL, FE TPG YQPYALPL, FEWTPGWYQJYALPL, FEWTPGYYQPYALPL and FEWTPGYYQJYALPL. An especially preferred embodiment is one having the substitution patterns just described, but comprising 21 amino acid residues. Particularly preferred is the peptide comprising the sequence of amino acids Z 12 Z 13 Z 14 Z 15 Z 16 Z 17 Z 18 Z 19 Z 20 Z 21 Z 22 Z 11 Z 7 Z 8°- Z 5 YZ 6 Z 9 Z 10 L ' w *h ere Z 8 ^ s Y, W or F; Z 11 is V, L, I, E, P, G, Y, M, T, or, D; Z 12 is A, D, E, F, G, K, Q, S, T, V, or Y; Z 13 is A, D, G, I, N, P, S, T, V, or ; Z 14 is A, D, G, L, N, P, S, T, W, or Y; Z 15 is A, D, E, F, L, N, R, V, or Y; Z 16 is A, D, E, Q, R, S, or T; Z 17 is H, I, L, P, S, T, or, ; Z 18 is A, E, F, K, N, Q, R, S, or Y; Z 19 is D, E, F, Q, R, T, or W; Z 20 is A, D, P, S, T, or W; Z 21 is A, D, G, K, N, Q, S, or T; and Z 22 is A, E, L, P, S, T, V or Y. More preferably, Z 8 is Y, W or F; Z l λ is V, L, I, E, P, G, Y, M, T, or, D; Z 12 is D , E , Q , s, T , v, or Y ; Z 13 is A, D, G, I, N, S, T or V; Z 14 is A , G , L , N , P , s , , or Y ' Z 15 is D, E, F, L, V, or Y; z ιβ is D , R, S or T ; z 17 is H , P , s , or W; Z 18 is E, F, N R , Q , or s; z 19 is D , E , F , Q , or W ; Z 20 is S, T, or ; Z 21 is D, G, K, N, Q, S, or T; and Z 22 is A, E, P, S, or Y. Particularly preferred peptides include TANVSSFEWTPGYWQPYALPL; SWTDYGYWQPYALPISGL; ETPFTWEESNAYYWQPYALPL; ENTYSPNWADSMYWQPYALPL; SVGEDHNFWTSEYWQPYALPL; and DGYDRWRQSGERYWQPYALPL. In a related embodiment, the present invention also provides peptides which bind to IL-lRtI, which are fourteen to forty or more amino acid residues in length, preferably fourteen to twenty-five amino acid residues in length, and which comprise a core amino acid sequence FTWEESNAYYWQJY-NH 2 . According to another embodiment, the invention provides peptides which bind to IL-lRtI, which are seven to forty or more amino acid residues in length, preferably seven to twenty-five amino acid residues in length, and which comprise a core sequence of amino acids Z 23 NZ 2 SZ 25 Z 26 Z 27 Z 28 Z 29 Z 30 L where Z 23 is D or Y; Z 24 is D or S; Z 25 is S or W; Z 26 is S or Y; Z 27 is D or V; Z 28 is S or W; Z 29 is F or L; and Z 30 is D or L. A further embodiment of the present invention provides peptides which bind to the IL-lRtI, which are '11 to 40 amino acids in length, which comprise the core seque ce of amino acids Z 31 XZ 41 Z 32 Z 33 Z 3 Z 35 Z 36 Z 42 Z 37 Z 38 , where each letter represents the standard one letter abbreviation for an amino acid or an analog thereof; X is selected from the group of natural or unnatural amino acids; Z 31 is selected from phenylalanine, tyrosine, 1-naphthylalanine ("INap") , 2- naphthylalanine ("2Nap") , p-benzoyl-L-phenylalanine ("Bpa") , tryptophan, histidine, homophenylalanine, 3-pyridylalanine ("Pya") , thienylalanine ("Tha") , benzothienylalanine ("Bta") , cyclohexylalanine ("Cha") , phenylglycine, D-phenylalanine, tetrahydroisoquinoline ("Tiq") tetrahydro-β-carboline ("The") , D-des-aminophenylalanine, and L-des-aminophenylalanine, and substituted amines thereof; Z 32 is a natural or unnatural amino acid; Z 33 is selected from proline, azetidine, sarcosine, alanine, D-proline, glycine, N-methylalanine ("N- MeAla") and pipecolic acid ("Pec") ; Z 34 is selected from glycine, asparigine, any D-amino acid, sarcosine, and aminoisobutyric acid, represented by Sar and Aib, respectively; Z 35 is a natural or unnatural amino acid; Z 36 is selected from tyrosine, phosphotyrosine (denoted "-pY-") , phenylalanine, tryptophan, 1-naphthylalanine and p-benzoyl-L- phenylalanine, 4-nitrophenylalanine, 4-aminophenylalanine, 4- methoxyphenylalanine and tetrahydro-β-carboline; Z 37 is selected from proline or azetidine, represented as J; Z 38 is selected from tyrosine, tyrosinamide, substituted tyrosinamide, p-benzoyl-L-phenylalanine, phenylalanine, 4- aminophenylalanine, 4-methoxyphenylalanine, 3-pyridylalanine and 4-nitrophenylalanine, Z 41 is selected from tryptophan, 4- nitrophenylalanine, phenylalanine, 1-naphthylalanine, 4- aminophenylalanine, 4-methoxyphenylalanine, and tetrahydro-β- carboline, and Z 42 is selected from glutamine and α-N- methylglutamine. More preferred are those peptides wherein Z 32 is selected from alanine, threonine, valine, allothreonine, isoleucine, serine, and norleucine ("nle") ; Z 34 is selected from glycine, D-aspartic acid, D-lysine, D-phenylalanine, N- Methyl-D-alanine, D-alanine, D-valine, sarcosine, and aminoisobutyric acid, represented by Sar and Aib, respectively; Z 35 is selected from the group consisting of tyrosine, phosphotyrosine (denoted "-pY-") , phenylalanine, tryptophan, 1-naphthylalanine and p-benzoyl-L-phenylalanine, 4-nitrophenylalanine (4-N0 2 -Phe) , 4-aminophenylalanine (4-NH 2 - Phe) , 4-methoxyphenylalanine (4-CH 3 0-Phe) , methoxytyrosine ((CH 3 0)Y), tetrahydro-j3-carboline and 3-pyridylalanine; Z 41 is tryptophan, phenylalanine, 4-nitrophenylalanine and 1- naphthylalanine; and Z 42 is glutamine. Particularly preferred peptides are those selected from the group consisting of the following peptides and amides and esters thereof: FEWTPGYWQPY-NH 2 ; FEWTPGYWQJY-NH 2 ; FEWTPGWYQJY-NH 2 ; AcFEWTPGWYQJY-NH 2 ; FEWTPGW-pY-QJY-NH 2 ; FAWTPGYWQJY-NH 2 ; FEWAPGYWQJY-NH 2 ; FEWVPGYWQJY-NH 2 ; FEWTPGYWQJY-NH2; AcFEWTPGYWQJY-NH 2 ; FEWTPaWYQJY-NH 2 ; FEWTP- Sar-WYQJY-NH 2 ; FEWTPGYYQPY-NH 2 ; FEWTPGWWQPY-NH 2 ; FEWTPNYWQPY- NH 2 ; FEWTPvYWQJY-NH 2 ; FEWT-Pec-GYWQJY-NH 2 ; FEWTP-Aib-YWQJY- NH 2 ; FEWT-Sar-GYWQJY-NH 2 ; FEWTPGYWQPYALPL; FEWTPGYYQJ-Bpa-NH 2 ; AcFEWTPGYYQJ-Bpa-NH 2 , FEWTPGY-Bpa-QJY-NH 2 ; AcFEWTPGY-Bpa-QJY-NH 2 ; FEWTPG-Bpa-YQJY-NH 2 ; AcFEWTPG-Bpa-YQJY-NH 2 ; Bpa-EWTPGYYQJY-NH 2 ; AcBpa-EWTPGYYQJY-NH 2 ; lNap-EWTPGYYQJY-NH 2 ; YEWTPGYYQJY-NH 2 ; FEWVPGYYQJY-NH 2 ; FEWTPsYYQJY-NH 2 ; FEWTPnYYQJY-NH 2 ; (Me 3 N)lNap-EWTPaWYQJY; AcFEWTPaWYQJY; FEWTPnYYQJY; AcFEWTPGYYQJY, (Me 3 N) F-EWTPGWYQJY, AcFEWTPaYYQJY; Ac2Nap-EWTPaYWQJY; (Me 3 N) 2Nap-EWTPaWYQJY; FEWTPGWYQJY; AcWEWTPaYWQJY; Ac(CH 3 0)Y-EWTPaYWQJY; Ac(4-N0 2 ) F-EWTPaYWQJY; (Me 2 N)F-EWTPaWYQJY; (Me 2 N)F-EWTPaWYQJY; AcYEWTPaYWQJY; (Me 3 N)Bta-EWTPaWYQJY; AcFEWTPaWYQJY; (Me 3 N)F-EWTPaQJY; AcFEWTPaFWQJY; HO-(R) -F-EWTPGWYQJY; (Me 3 N) 2Nap-EWTPaWY-(NMe)Q-JY; FEW-Nle-PGYWQJY; AcFEWTPdWYQJY; AcFEWTPaY-(4NH 2 ) F-QJY; FEW-alloThr-PGYWQJY; AcFEWTPa-(4-N0 2 ) F-WQJY; AcFEWTPkWYQJY; AcFEWTPa-(4-NH 2 )J-YQJY; Ac-FQWTPaYWQJY; (Me 3 N) ha-EWTPaWYQJY; AcPya-EWTPaYWQJY; AcFEWTPa-(4-NH 2 )F-WQJY; NH 2 (=0) F-EWTPaYWQJY; Ac-Thc-EWTPaYWQJY; AcFEWTPa-(CH 3 0) -WYQJY; HO-(S)-F-EWTPGWYQJY; AcF-(CH 3 0)E-WTPaYWQJY; ACFEWTPaYWQJF; AcFEWTPaY-(4-N0 2 ) F-QJY; AcFEWTPaW-(CH 3 0) Y-QJY; AcFEWTP-(NMe-a)-WYQJY; AcFEWTPaYWQJ-(4-NH 2 ) F; FEWTJGYWQJY; AcFMWTPaYWQJY; AcFDWTPaYWQJY; AcFEWTPa-(CH 3 0)Y-YQJY; AcFEWT-(NMe-A) -aWYQJY; AcFEWTPfWYQJY; AcFEWTPaY-Pya-QJY; AcFHWTPaYWQJY; AcFEWIPaYWQJY; AcfEWTPaYWQJY; FEWSPGYWQJY; FEWTAGYWQJY; FEWTpGYWQJY; ACHEWTPaYWQJY; Ac-hmoF-EWTPaYWQJY; AcFEWAPpYWQJY; AcFEW-Nle-PaYWQJY; AcFEYTpaYWQJY; AcFEWTPa-Thc-YQJY; AcFE-(4-N0 2 ) F-TPaYWQJY; des(NH 2 ) F-EWTPaWYQJY; FE-lNap-TPGWYQJY; AcFEFTPaYWQJY; AcFEWTPaYWQJY-(CH 3 0)Y; AcFEWTPaY-Thc-QJY; AcFEWTPaWYQJ-Pya; Ac-Tiq-EWTPaWYQJY; Ac-Cha-EWTPaWYQJY; and AcFE-Pya-TPaYWQJY, where AcF is acetylated phenylalanine, Y-NH 2 is tyrosinamide, -pY- is phosphotyrosine, -Sar- is sarcosine, -Pec- is pipecolic acid, -Aib- is arαinoisobutyric acid, INap is 1- naphthylalanine, 2Nap is 2-naphthylalanine, Pya is pyridylalanine; Cha is cyclohexylalanine, NMe-A is N- methylalanine, Tha is thienylalanine, Bta is benzothienylalanine, The is tetrahydro-β-carboline, allothr is allothreonine, having the opposite stereochemistry from threonine at the C3 position, Tiq is tetrahydroisoquinoline, hmoF is homophenylalanine, (4-NH 2 )F is 4-aminophenylalanine, (4-N0 2 )F is 4-nitrophenylalanine, Nle is norleucine, (CH 3 ))Y is methoxytyrosine, Bpa is p-benzoyl-L-phenylalanine and AcBpa is acetylated p-benzoyl-L-phenylalanine. The present invention also provides conjugates of these peptides and derivatives and peptidomi etics of the peptides that retain the property of IL-lRtI binding but, by virtue of the conjugated compound, act either as an agonist or antagonist of IL-lRtI or direct a cytotoxic or other therapeutic agent to cells that express IL-lRtI. The compounds described herein are useful for the prevention and treatment of diseases involving improper production of or response to IL-1 utilizing the novel compounds of the invention. Thus, the present invention also provides a method of treatment, wherein a patient having a disorder that is susceptible to treatment with an IL-1 inhibitor receives, or is administered, a therapeutically effective dose or amount of a compound of the present invention. The invention also provides for pharmaceutical compositions comprising one or more of the compounds described herein and a physiologically acceptable carrier. These pharmaceutical compositions can be in a variety of forms including oral dosage forms, as well as injectable and infusible solutions. The present invention also provides conjugates of these peptides and derivatives and peptidomimetics of the peptides that retain the property of IL-lRtI binding but, by virtue of the conjugated compound, act either as an agonist or antagonist of IL-lRtI or direct a cytotoxic or other therapeutic agent to cells that express IL-lRtI. DESCRIPTION OF THE PREFERRED EMBODIMENT I. Definitions and General Parameters The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. "Pharmaceutically acceptable salts" refer to the non-toxic alkali metal, alkaline earth metal, and ammonium salts commonly used in the pharmaceutical industry including the sodium, potassium, lithium, calcium, magnesium, barium, ammonium, and protamine zinc salts, which are prepared by methods well known in the art. The term also includes non-toxic acid addition salts, which are generally prepared by reacting the compounds of this invention with a suitable organic or inorganic acid. Representative salts include the hydrochloride, hydrobro ide, sulfate, bisulfate, acetate, oxalate, valerate, oleate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napsylate, and the like. "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases and which are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, menthanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. For a description of pharmaceutically acceptable acid addition salts as prodrugs, see Bundgaard, H. , ed. , (1985) Design of Prodrugs , Elsevier Science Publishers, Amsterdam. "Pharmaceutically acceptable ester" refers to those esters which retain, upon hydrolysis of the ester bond, the biological effectiveness and properties of the carboxylic acid or alcohol and are not biologically or otherwise undesirable. For a description of pharmaceutically acceptable esters as prodrugs, see Bundgaard, H. , ed. , (1985) Design of Prodrugs , Elsevier Science Publishers, Amsterdam. These esters are typically formed from the corresponding carboxylic acid and an alcohol. Generally, ester formation can be accomplished via conventional synthetic techniques. (See, e.g., March Advanced Organic Chemistry, 3rd Ed., John Wiley & Sons, New York (1985) p. 1157 and references cited therein, and Mark et al . Encyclopedia of Chemical Technology, John Wiley & Sons, New York (1980).) The alcohol component of the ester will generally comprise (i) a C 2 -C 12 aliphatic alcohol that can or can not contain one or more double bonds and can or can not contain branched carbon chains or (ii) a C 7 -C 12 aromatic or heteroaromatic alcohols. This invention also contemplates the use of those compositions which are both esters as described herein and at the same time are the pharmaceutically acceptable acid addition salts thereof. "Pharmaceutically acceptable amide" refers to those amides which retain, upon hydrolysis of the amide bond, the biological effectiveness and properties of the carboxylic acid or amine and are not biologically or otherwise undesirable. For a description of pharmaceutically acceptable amides as prodrugs. See Bundgaard, H. , supra . These amides are typically formed from the corresponding carboxylic acid and an amine. Generally, amide formation can be accomplished via conventional synthetic techniques. (See, e.g., March Advanced Organic Chemistry, 3rd Ed., John Wiley & Sons, New York (1985) p. 1152 and Mark et al. Encyclopedia of Chemical Technology, John Wiley & Sons, New York (1980).) This invention also contemplates the use of those compositions which are both amides as described herein and at the same time are the pharmaceutically acceptable acid addition salts thereof. "Pharmaceutically or therapeutically acceptable carrier" refers to a carrier medium which does not interfere with the effectiveness of the biological activity of the active ingredients and which is not toxic to the host or patient. "Stereoisomer" refers to a chemical compound having the same molecular weight, chemical composition, and constitution as another, but with the atoms grouped differently. That is, certain identical chemical moieties are at different orientations in space and, therefore, when pure, has the ability to rotate the plane of polarized light. However, some pure stereoisomers may have an optical rotation that is so slight that it is undetectable with present instrumentation. The compounds of the instant invention may have one or more asymmetrical carbon atoms and therefore include various stereoisomers. All stereoisomers are included within the scope of the invention. "Therapeutically- or pharmaceutically-effective amount" as applied to the compositions of the instant invention refers to the amount of composition sufficient to induce a desired biological result. That result can be alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. In the present invention, the result will typically involve a decrease in the immunological and/or inflammatory responses to infection or tissue injury. Amino acid residues in peptides are abbreviated as follows: Phenylalanine is Phe or F; Leucine is Leu or L; Isoleucine is lie or I; Methionine is Met or M; Valine is Val or V; Serine is Ser or S; Proline is Pro or P; Threonine is Thr or T; Alanine is Ala or A; Tyrosine is Tyr or Y; Histidine is His or H; Glutamine is Gin or Q; Asparagine is Asn or N; Lysine is Lys or K; Aspartic Acid is Asp or D; Glutamic Acid is Glu or E; Cysteine is Cys or C; Tryptophan is Trp or W; Arginine is Arg or R; and Glycine is Gly or G. Amino acids acetylated at the amino group will possess the prefix "Ac". Thus, acetylated phenylalanine will be represented by AcF. Similarly, carboxamide amino acids will possess the suffix "NH 2 ". In addition to peptides consisting only of naturally-occurring amino acids, peptidomimetics or peptide analogs are also provided. Peptide analogs are commonly used in the pharmaceutical industry as non-peptide drugs with properties analogous to those of the template peptide. These types of non-peptide compound are termed "peptide mimetics" or "peptidomimetics" (Fauchere, J. (1986) Adv . Drug Res . 15:29; Veber and Freidinger (1985) TINS p.392; and Evans et al . (1987) J . Med . Chem . 30:1229, which are incorporated herein by reference) . Peptide mimetics that are structurally similar to therapeutically useful peptides may be used to produce an equivalent or enhanced therapeutic or prophylactic effect. Generally, peptidomimetics are structurally similar to a paradigm polypeptide (i.e., a polypeptide that has a biological or pharmacological activity) , such as naturally-occurring receptor-binding polypeptide, but have one or more peptide linkages optionally replaced by a linkage selected from the group consisting of: -CH 2 NH-, -CH 2 S-, -CH 2 -CH 2 -, -CH=CH- (cis and trans), -C0CH 2 -, -CH(0H)CH 2 -, and -CH 2 S0-, by methods known in the art and further described in the following references: Spatola, A.F. in CHEMISTRY AND 13 BIOCHEMISTRY OF AMINO ACIDS, PEPTIDES, AND PROTEINS, B. Weinstein, eds.. Marcel Dekker, New York, p. 267 (1983); Spatola, A.F., Vega Data (March 1983), Vol. 1, Issue 3, Peptide Backbone Modifications (general review) ; Morley, Trends Pharm Sci (1980) pp. 463-468 (general review); Hudson, D. et al . , (1979) Int J Pept Prot Res 14:177-185 (-CH 2 NH-, CH 2 CH 2 -) ; Spatola et al . , (1986) Life Sci 38:1243-1249 (-CH 2 -S) ; Hann (1982) J . Chem . Soc . Perkin Trans. I 307-314 (-CH-CH-, cis and trans) ; Almquist et al . , (1980) J Med Chem 23:1392-1398 (-C0CH 2 -) ; Jennings-White et al . , (1982) Tetrahedron Lett 23:2533 (-C0CH 2 -) ; Szelke et al . , (1982) European Appln. EP 45665 CA: 97:39405 (1982) (-CH(OH) CH 2 ~) ; Holladay et al . , (1983) Tetrahedron Lett 24:4401-4404 (-C(OH) CH 2 -) ; and Hruby (1982) Life Sci 31:189-199 (-CH 2 -S-) ; each of which is incorporated herein by reference. A particularly preferred non-peptide linkage is -CH 2 NH-. Such peptide mimetics may have significant advantages over polypeptide embodiments, including, for example: more economical production, greater chemical stability, enhanced pharmacological properties (half-life, absorption, potency, efficacy, etc.), altered specificity (e . g. , a broad-spectrum of biological activities), reduced antigenicity, and others. Labeling of peptidomimetics usually involves covalent attachment of one or more labels, directly or through a spacer (e.g., an amide group), to non-interfering position(s) on the peptidomimetic that are predicted by quantitative structure-activity data and/or molecular modeling. Such non-interfering positions generally are positions that do not form direct contacts with the macromolecules(s) (e . g. , immunoglobulin superfamily molecules) to which the peptidomimetic binds to produce the therapeutic effect. Derivitization (e.g., labeling) of peptidomimetics should not substantially interfere with the desired biological or pharmacological activity of the peptidomimetic. Generally, peptidomimetics of receptor-binding peptides bind to the receptor with high affinity and possess detectable biological activity (i.e., are agonistic or antagonistic to one or more receptor-mediated phenotypic changes) . Abbreviations of some of the nonnatural amino acids or amino acid analogs, used herein, include "Aib" for aminoisobutyric acid, "Sar" for sarcosine,"Pec" for pipecolic acid, "lNap" for 1- naphthylalanine, "2Nap" for 2-naphthylalanine, Pya for 3- pyridylalanine, Tiq for tetrahydorisoquinoline, Cha for cyclohexylalanine, Tha for thienylalanine, Bta for benzothienylalanine, The for tetrahydro-β-carboline, allothr for allothreonine, hmoF for homophenylalanine, NMe-A for N- methylalanine, and "Bpa" for p-benzoyl-L-phenylalanine. Systematic substitution of one or more amino acids of a consensus sequence with a D-amino acid of the same type (e . g. , D-lysine in place of L-lysine) may be used to generate more stable peptides. In addition, constrained peptides comprising a consensus sequence or a substantially identical consensus sequence variation may be generated by methods known in the art (Rizo and Gierasch (1992) Ann . Rev . Biochem . 61: 387, incorporated herein by reference); for example, by adding internal cysteine residues capable of forming intramolecular disulfide bridges which cyclize the peptide. Such D-amino acids are abbreviated by the lower case single letter abbreviations previously described herein, e . g. , where "A" represents L-alanine and "a" represents D-alanine. II. Overview The present invention provides compounds that bind to the IL-lRtI. These compounds include "lead" peptide compounds and "derivative" compounds constructed so as to have the same or similar molecular structure or shape as the lead compounds but that differ from the lead compounds either with respect to susceptibility to hydrolysis or proteolysis and/or with respect to other biological properties, such as increased affinity for the receptor. The present invention also provides compositions comprising an effective IL-lRtI binding, IL-1 blocking compound, and more particularly a compound, that is useful for treating disorders associated with the overexpression of IL-1. In general, the peptides of the present invention will have strong binding properties to the Interleukin-1 type I receptor ("IL-lRtI") . Specifically, the peptides will be characterized as having a binding affinity to IL-lRtI as measured by an IC50 of about 2.5 mM or less, typically, about 100 μM or less, and preferably, 20 μM or less. Additionally, the peptides of the present invention may be relatively small. Typically, the peptides have a molecular weight of less than about 5000 kilodaltons, and preferably, less than about 3000 kilodaltons. III. Random Peptide Diversity Generating Systems Initial lead peptide compounds were identified using random peptide diversity generating systems including the "peptides on phage" and "peptides on plasmids" systems discussed above and described in U.S. Patent No. 5,270,170, and co-pending U.S. application Serial Nos. 718,577, and 07/847,567, filed March 5, 1992. The random peptides were designed to be eight to twelve amino acid residues in length, and one system employed fixed cysteine residues at each end of the random peptide to facilitate the formation of cyclic peptides. To generate the collection of oligonucleotides that encode the random peptides, the codon motif (NNK)x, where N was nucleotide A, C, G, or T (equimolar; depending on the methodology employed, other nucleotides can be employed), K is G or T (equimolar) , and x was 6 (for the cyclic library—the other two terminal codons were cysteine codons) , 8, 10, or 12; was used in the synthesis of the oligonucleotides. Those of skill in the art will recognize that the NNK motif encodes all of the amino acids, encodes only one stop codon, and reduces codon bias. There are 32 possible codons resulting from the NNK motif: 1 for each of 12 amino acids, 2 for each of 5 amino acids, 3 for each of 3 amino acids, and only one of the three stop codons. In these initial systems, the random peptides were presented as part of a fusion protein comprising either the pill or pVIII coat protein of a phage fd derivative (peptides on phage) or the lac repressor DNA binding protein (peptides on plasmids) . The fusion proteins, along with the DNA encoding the fusion proteins, were "panned" on immobilized IL-lRtI. The panning process involved multiple rounds of incubating the fusion proteins with the immobilized receptor, collecting the fusion proteins that bound to the receptor (along with the accompanying DNA) , and amplifying the fusion proteins collected. Typically after three rounds of panning, the fusion proteins and accompanying DNA were isolated and cultured to produce fusion protein preparations for an ELISA to determine if the fusion protein bound specifically to the receptor. This assay was carried out similarly to the panning, except that after removing unbound fusion proteins, the wells were treated with rabbit anti-phage antibody (or with anti-lac antibody for the peptides on plasmids system) , then with alkaline phosphatase-conjugated goat anti-rabbit antibody, and then the amount of alkaline phosphatase in each well was determined by standard methods. By comparing test wells with control wells (no receptor) , one can determine whether the fusion proteins bind to the receptor specifically. Fusion proteins found to bind specifically to the receptor were then tested in an IL-lα blocking assay. The blocking assay was carried out in similar fashion to the ELISA , except that IL-lα was added to the wells before the fusion protein (the control wells were of two types: (1) no receptor; and (2) no IL-lα) . Fusion proteins for which the binding to the receptor was blocked by IL-lα contain peptides in the random peptide portion that are preferred compounds of the invention. Several forms of the Type I IL-1 receptor were used in the panning and ELISA procedures and IC 50 determinations. For example, radiolabelled monovalent receptor was prepared by expressing soluble receptor fused with the 7 amino acid substrate sequence for protein kinase A. The receptor was then labelled using protein kinase A and 33 P or 32 P-ATP. See, Li, B. L. , et al., Creation of phosphorylation sites in proteins: construction of a phosphorylatable human interferon alpha, Proc . Natl Acad . Sci . 86(2) :558-562. Additionally, an immobilized receptor useful in the panning and ELISA procedures was produced in recombinant host cells in a truncated form comprising the complete extracellular domain (as determined by hydrophobicity studies) of IL-lRtI (amino acids 1 to 336 of the sequence reported by Chua and Gubler, 1989, Nuc . Acids Res . 17 (23) :10114, incorporated herein by reference) . This truncated receptor molecule can be produced in a variety of different forms and host cells. One useful form of the receptor is constructed by expressing the receptor as a soluble protein in baculovirus transformed host cells using standard methods; another useful form is constructed with a signal peptide for protein secretion and for glycophospholipid membrane anchor attachment (this form of anchor attachment is called "PIG-tailing;" see Caras and Weddell (1989) Science 243:1196-1198, and Lin et al . , (1990) Science 249:677-679, each of which is incorporated herein by reference) . Using the latter system, one can cleave the receptor from the surface of the cells expressing the receptor and collect the cleaved receptor quite easily. Several bivalent forms of the receptor were also prepared for use in the identification of peptides capable of interacting with the I1-1 receptor. A bivalent receptor-antibody complex was generated by mixing 33 P labeled receptor with an anti-IL-lRtl antibody followed by the addition of excess unlabeled receptor. Similarly, a bivalent receptor was obtained by mixing an excess of the receptor with 125 I labeled antibody, and then purifying the receptor by passing it over an Abl79 column (if one is using the PIG-tailed form of the receptor, then one can use an antibody that binds to the HPAP residue that remains attached to the receptor after secretion and cleavage) . Another bivalent receptor was constructed by linking the extracellular portion of the Type I IL-IR through its C-terminus to the Fc portion of a human IgG molecule. The recombinant receptor protein was immobilized using the following methodology. Microtiter plates were coated with an anti-IL-lRtl antibody that does not block IL-lα binding to IL-lRtI and then the wells containing the immobilized receptor were treated with bovine serum albumin (BSA) to block non-specific binding. The receptor was added to the coated wells of the microtiter plate, which were then washed to remove unbound receptor. Often, the receptor was added only to alternate rows of the microtiter plate; the BSA-blocked wells in the "blank" rows served as useful negative controls to determine whether a receptor-specific reaction was creating the observed results. Fusion protein preparations were then added to the wells and incubated to allow binding to the receptor to occur; then, the wells were washed to remove unbound fusion proteins. With the above systems, a number of different fusion proteins were discovered that bind to the IL-lRtI, but that binding did not appear to be blocked by IL-lα at a concentration of about 12 μM. The DNA encoding the fusion proteins that bound to the receptor was sequenced to determine the sequence of the random peptide that the fusion proteins contained. These peptides, together with similar peptides isolated using different libraries (discussed below) are shown in Table 1, below. Table 1 Fusion Protein Random Peptide Sequence Rl WWTDTGLW Rll WWTDDGLW S4 WWDTRGLWVWTI DB29 FWGNDGIWLESG S14 DWDQFGLWRGAA NU1 RWDDNGLWVWL Til SGMWSHYGIWMG T12 GGRWDQAGLWVA MCI KLWSEQGIWMGE CYC1 CWSMHGLWLC F17 GCWDNTGIWVPC IL1 DWDTRGLWVY IL3 SLWDENGAWI IL4 KWDDRGLWMH IL6 QAWNERGLWT IL7 QWDTRGLWVA IL8,11E WNVHGIWQE IL9 SWDTRGLWVE IL12,17 DWDTRGLWVA IL13 SWGRDGLWIE IL16 EWTDNGLWAL IL19 SWDEKGLWSA IL20 SWDSSGLWMD The peptides in Table 1 are characterized by the motif "WXXXGZ- j^ W" where each amino acid is indicated by standard one letter abbreviation; each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids; and Z is L, I, A, or Q. More preferably, the core sequence of amino acids will be comprise WZ 2 XXGZ 2 W where X can be selected from any one of the 20 genetically coded L-amino acids; Z λ is L, I, A, or Q; and Z 2 is D, G, N, S, or T. In a more preferred embodiment, the core sequence of amino acids will comprise WZ 2 Z 3 Z 4 GZ 1 'W where Z is L, I, A, or Q; Z 2 is D, G, N, S, or T; Z 3 , is D, E, H, M, N, Q, R, S, T, or V; and Z 4 is A, D, F, H, K, N, Q, R, T, or Y. Most preferably, the core sequence of amino acids comprise WZ^^^Z- L W where Z is L or I; Z 2 is D, S, or T; Z 3 is D, E, or T; and Z 4 is D, H, N, R, or T. An especially preferred embodiment is one having the substitution patterns just described, but comprising 8, 10, or 12 amino acid residues. An especially preferred peptide has the sequence SWDTRGLWVE. These peptides are valuable due to their ability to bind specifically with the IL-IR without blocking the IL-lα binding site on the receptor. The peptides of the present invention can be conjugated to compounds that do bind to the IL-lα binding site of an IL-IR to construct compounds with an affinity for the IL-IR greater than either of the compounds of which the conjugate is composed. The discovery of these peptides also facilitates the identification of peptides that do bind to the same site on IL-IR as IL-lα, because one can bias the library or panning procedure to eliminate peptides with this "non-blocking" motif. For instance, one can make a library with no tryptophan residues in the random peptide or one can pan a library using receptor immobilized with an anti-IL-IR antibody that blocks binding of peptides with this motif but does not block IL-1 binding. One could also pan in the presence of high concentrations of the peptide. Several new libraries of random peptides were constructed in a manner designed to minimize the production of fusion proteins comprising the "WXXXGZ- j^ W" motif. These libraries were characterized by the use of the codon motif "NNW," where W is nucleotide A or T, in codons two and eight in synthesizing the oligonucleotide encoding the random peptide. The resulting peptides thus did not contain a methionine (M) or a tryptophan (W) at positions two and eight of the random peptide portion of the fusion protein. Panning of these libraries yielded fusion proteins Til, T12, and F17 in Table 1, above, together with the fusion protein T6, which comprises the peptide "RLVYWQPYSVQR". Phage bearing the fusion protein T6 bound specifically to IL-lRtI, and binding of the phage was inhibited by IL-lα. The T6 peptide was synthesized on a peptide synthesizer (Example 1, below) , and the synthetic free peptide was tested and found to compete with IL-lα in binding to the IL-IR at micromolar concentration (see Example 3) . A. Peptides Possessing the OPY or OPY-like Motif The T6 peptide sequence, above, then served as the basis for the construction of another peptide library designed to contain a high frequency of derivatives of the T6 peptide. This library was synthesized so as to favor the production of peptides that differ from the T6 peptide in only a few residues. This approach involved the synthesis of an oligonucleotide with the T6 random peptide coding sequence, except that rather than using pure preparations of each of the four nucleoside triphosphates in the synthesis, mixtures of the four nucleoside triphosphates were used so as to generate derivatives of the T6 peptide coding sequence. This library was prepared and panned as above, and the peptide sequences obtained are shown in Table 2, below, together with the T6 sequence. IC50 values are indicated symbolically by the symbols "-", "+", and "++". For example, those peptides which showed IC50 values in excess of 100 μM are indicated with a "- ". Those peptides which give IC50 values of less than or equal to 100 μM are given a "+", while those which give IC50 values of 500 nM or less are indicated with a "++". Those peptides which give IC50 values at or near the cutoff point for a particular symbol are indicated with a hybrid, e.g. "+/- ". Those peptides for which IC50 values were not determined are listed as "N.D". Table 2 Fusion Protein Random Peptide Sequence J -50- 2H2 SHLYWQPYSVQ + H3 TLVYWQPYSLQT + 3H9 , 11 RGDYWQPYSVQS + 3H5 VHVYWQPYSVQT + 3H2 RLVYWQPYSVQT + 3H1 , 6 , 12 SRVWFQPYSLQS + 3H7 NMVYWQPYSIQT + 3H10 SWFWQPYSVQT + 3H4 TFVYWQPYALPL + 2H11 TLVYWQPYSIQR + T6 RLVYWQPYSVQR + Dl SPVFWQPYSIQI + D2 WIEWWQPYSVQS + D3 SLIYWQPYSLQM + D13 TRLYWQPYSVQR + D15 RCDYWQPYSVQT + D18 MRVFWQPYSVQN + D19 KIVYWQPYSVQT + D20 RHLYWQPYSVQR + 2H6 ALVWWQPYSEQI + 3H8 SRVWFQPYSLQS ' Unless otherwise indicated, IC^ determinations were conducted using soluble peptide . Results marked with * were obtained using the immobilized PIG-tailed Type I IL-IR. Table 2 shows that a general structure for these compounds is defined by Z 7 XQZ 5 YZ 6 XX where X can be selected from any one of the 20 genetically coded L-amino acids; Z 5 is P or Aze (or J) where Aze is azetidine; Z 6 is S, A V, or L; and Z 7 is Y, W, or F. In addition, screening of a 10-mer library on PVIII in the presence of a known blocking peptide, SWDTRGLWVE resulted in the identification of the following peptides: Table 3 Peptide IC 50 WEQPYALPLE + REYEQPYALW EEWAQPYAFL GSWEQPYAMV AWYGPSNLPV The results of screening of various other libraries (for example, 70:10:10:10; fixed-sliding libraries and extended/mutagenized libraries which were screened using standard elution conditions and tested under standard or low receptor density conditions) are shown below: Table 4 Library Based on RLVYWOPYSVOR with 50% NNK Peptide IC 50 QLVWWQPYSVQR + DLRYWQPYSVQV + ELVWWQPYSLQL + DLVWWQPYSVQW + NGNYWQPYSFQV + ELVYWQPYSIQR + WSNYWQPYSVQP +/- QYVYWQPLSVQV ELMYWQPYSVQE N.D. NLLYWQPYSMQD N.D. Table 5 Library Based on XXXXXXPYSVOR Peptide IC 50 GYEWYQPYSVQR + SRVWYQPYSVQR + LSEQYQPYSVQR + GGGWWQPYSVQR + VGRWYQPYSVQR + VHVYWQPYSVQR + QARWYQPYSVQR + VHVYWQPYSVQT + RSVYWQPYSVQR + TRVWFQPYSVQR + GRIWFQPYSVQR + GRVWFQPYSVQR ARTWYQPYSVQR + GRLWWQPYSVQR +/" HRIWWQPYSVQR +/" GRVWWQPYSVQR +/" ARVWWQPYSVQM N.D. RLMFYQPYSVQR N.D. ESMWYQPYSVQR N.D. HFGWWQPYSVHM N.D. ARFWWQPYSVQR N.D. Table 6 Library Based on "RLVYWO XXXXXX Peptide IC 50 RLVYWQ PYAPIY + RLVYWQ PYSYQT + RLVYWQ PYSLPI + RLVYWQ PYSVQA + RLVYWQ PWAPIW Table 7 Library Based on "SRVWYO XXXXXX" Peptide IC 50 SRVWYQ PYAKGL + SRVWYQ PYAQGL + SRVWYQ PYAMPL + SRVWYQ PYSVQA + SRVWYQ PYSLGL + SRVWYQ PYAREL + SRVWYQ PYSRQP + SRVWYQ PYFVQP +/- Table 8 Library Based on "XXXXXXPYALPL" Peptide IC -5,0 EYEWYQ PYALPL + IPEYWQ PYALPL + SRIWWQ PYALPL + DPLFWQ PYALPL + SRQWVQ PYALPL + IRSWWQ PYALPL + RGYWQ PYALPL + RLLWVQ PYALPL + EYRWFQ PYALPL + DAYWVQ PYALPL + WSGYFQ PYALPL + NIEFWQ PYALPL + TRDWVQ PYALPL + DSSWYQ PYALPL + IGNWYQ PYALPL + NLRWDQ PYALPL + LPEFWQ PYALPL + DSYWWQ PYALPL + RSQYYQ PYALPL + ARFWLQ PYALPL + NSYFWQ PYALPL + ESFWVQ PYALPL Table 9 Library Based on "RLVYWOPYSVOR" with 70-10-10-10 Mutagenesis Peptide IS 50 RFMYWQPYSVQR + AHLFWQPYSVQR + WGNWWQPYSVHR Table 10 Library Based on "XXOPYXXXX" Peptide IC 50 WWQPYALPL YYQPYALPL + YFQPYALGL + YFQPYALPF Table 11 Library Based on "XXXOPYXXXX" Peptide I£ 5 o YWYQPYALPL + RWWQPYATPL + GWYQPYALGF + YWYQPYALGL + IWYQPYAMPL + SNMQPYQRLS N.D. Table 12 Library Based on "TFVYWOPY XXXXXXXXXXXX" Peptide TFVYWQPY AVGLFAAETACN TFVYWQPY SVQMTITGKVTM TFVYWQPY SSHXXVPXGFPL TFVYWQPY YGNPQWAIHVRH TFVYWQPY VLLELPEGAVRA TFVYWQPY VDYVWPIPIAQV A library based on the following motif "XXXXXX(PG/GP)XXXXXX" where X represents any of the naturally occurring L-amino acids was also prepared. Screening of this library resulted in the identification of the peptide IMWFCQPGGACYSV which had an IC 50 of between 100 and 500 μM. The peptides-on-plasmid system was also employed to identify peptides capable of interacting with the IL-1 receptor. Using this technique, a plasmid containing the Lad gene with an oligonucleotide cloning site at its 3 '-end was constructed. Under the controlled induction by arabinose, a Lacl-peptide fusion protein was produced. This fusion retains the natural ability of Lad to bind to the Lac operator (LacO) . By installing two copies of LacO on the expression plasmid, the Lacl-peptide fusion binds tightly to the plasmid that encoded it. Because the plasmids in each cell contain only a single oligonucleotide sequence and each cell expresses only a single peptide sequence, the peptides become specifically associated with the DNA sequence that directed its synthesis. The cells of the library were gently lysed and the peptide-DNA complexes were exposed to a matrix of immobilized receptor to recover the complexes containing the active peptides. The associated plasmid DNA was then reintroduced into cells for amplification and DNA sequencing to determine the identity of the peptide ligands. Using this system, the following peptides capable of interacting with the IL-1 receptor were identified. Table 13 Library Based on "XXXOPYXXXXXX" using C-terminal lac Repressor System Peptide IC 50 GWYQPYVDGWR + RWEQPYVKDGWS + EWYQPYALGWAR + GWWQPYARGL + LFEQPYAKALGL + GWEQPYARGLAG + AWVQPYATPLDE + MWYQPYSSQPAE + GWTQPYSQQGEV + DWFQPYSIQSDE + PWIQPYARGFG + A library was also screened by panning against IL-1 receptor expressed by cells to identify the following peptides: Table 14 Peptide IC 50 RPLYWQPYSVQV + TLIYWQPYSVQI + RFDYWQPYSDQT + WHQFVQPYALPL N.D. When using random peptide generation systems that allow for multivalent ligand-receptor interaction, one must recognize that the density of the immobilized receptor is an important factor in determining the affinity of the ligands that bind to the immobilized receptor. At higher receptor densities (i.e., each anti-receptor antibody-coated well treated with 250 to 500 ng of receptor) , multivalent binding is more likely to occur (if at all) than at lower receptor densities (i.e., each anti-receptor antibody-coated well treated with 0.5 to 1 ng of the receptor). If multivalent binding is occurring, then one will be more likely to isolate ligands with relatively low affinity. Typically, one can identify lead compounds using a high density of immobilized receptor and then test the derivatives of the lead compound at lower receptor densities to isolate compounds with higher affinity for the receptor than the lead compound. By screening libraries under conditions of low receptor density, the following peptides were identified. 28 Table 15 Library Based on "XXXX VYWOPYSVO XXXX" with Low Density Receptor Peptide EWDS VYWQPYSVQ TLLR WEQN VYWQPYSVQ SFAD SDV VYWQPYSVQ SLEM YYDG VYWQPYSVQ VMPA Table 16 Library Based on "XXXXXX PYALPL" with Low Density Receptor Peptide IC 50 SDIWYQ PYALPL + QRIWWQ PYALPL + SRIWWQ PYALPL + RSLYWQ PYALPL + TIIWEQ PYALPL + WETWYQ PYALPL + SYDWEQ PYALPL + SRIWCQ PYALPL + EIMFWQ PYALPL + DYVWQQ PYALPL + Table 17 Library Based on "XXXXXX WYOPYALPL" with Low Density Receptor Peptide MDLLVQ WYQPYALPL GSKVIL WYQPYALPL RQGANI WYQPYALPL GGGDEP WYQPYALPL SQLERT WYQPYALPL ETWVRE WYQPYALPL KKGSTQ WYQPYALPL LQARMN WYQPYALPL EPRSQK WYQPYALPL VKQKWR WYQPYALPL LRRHDV WYQPYALPL RSTASI WYQPYALPL ESKEDQ WYQPYALPL EGLTMK WYQPYALPL EGSREG WYQPYALPL A "monovalent" phage approach was also used to identify peptides capable of binding the IL-1 receptor. In this approach, phage particles with only a single chimeric pill protein were created, thereby eliminating multivalent binding to immobilized receptor. Using this technique, the following peptides were identified. Table 18 Library Based on "XXXXXX PYALPL" with Monovalent Display Peptide IC 50 VIEWWQ PYALPL + VWYWEQ PYALPL + ASEWWQ PYALPL + FYEWWQ PYALPL + EGWWVQ PYALPL + WGEWLQ PYALPL + DYVWEQ PYALPL + AHTWWQ PYALPL + FIEWFQ PYALPL + WLAWEQ PYALPL + VMEWWQ PYALPL N.D. ERMWQ PYALPL N.D. To ascertain a rough indication of the affinity of the peptides, selected phage libraries were also screened using an affinity selection protocol. In brief, this protocol relies on the rapid association and dissociation between the peptide on an individual phage (either pill or pVIII) and the receptor. More specifically, for phage bearing low affinity ligands, the peptide on an individual pill (or pVIII) protein may be rapidly dissociating and reassociating, but the phage particle will not dissociate unless all the peptides on the phage are simultaneously in the unbound state. Dissociation of the phage can be initiated by addition of a competing peptide, which prevents rebinding of any individual peptide in the complex. The concentration (and affinity) of the competing peptide, as well as the time and temperature of elution can be varied to select for peptides of various affinities. Thus, to identify peptides capable of interacting with the IL-1 receptor, competition with a peptide or IL-1 was performed. This process is repeated typically for two rounds of panning. In subsequent rounds of panning, the competition temperature (4°C to ambient temperature) and time (15 to 30 minutes) as well as the temperature (4°C to ambient temperature) of the wash solutions can be altered to further select for peptides with high affinity. Table 19 Library Based on "XXXXXX PYALPL" with Peptide Competition Peptide J . '50 NXXWXX PYALPL N. D. WGNWYQ PYALPL N. D. TLYWEQ PYALPL N. D. VWRWEQ PYALPL N. .D. LLWTQ PYALPL N. ,D. SRIWXX PYALPL N. ,D. SDIWYQ PYALPL N. ,D. WGYYXX PYALPL N. ,D. TSGWYQ PYALPL N. .D. VHPYXX PYALPL N. .D. EHSYFQ PYALPL N. .D. XXIWYQ PYALPL N, .D. AQLHSQ PYALPL N, .D. WANWFQ PYALPL N. .D. SRLYSQ PYALPL N. .D. YYTWQQ PYALPL GVTFSQ PYALPL N.D. GWWYQ PYALPL SIVWSQ PYALPL N.D. YYSWQ PYALPL SRDLVQ PYALPL N.D. Table 20 Library Based on "XXXX VYWOPYSVO XXXX" with IL-1 Competition Peptide IC 50 HWGH VYWQPYSVQ DDLG + SWHS VYWQPYSVQ SVPE + WRDS VYWQPYSVQ PESA + TWDA VYWQPYSVQ KWLD N.D. TPPW VYWQPYSVQ SLDP N.D. YWSS VYWQPYSVQ SVHS N.D. Table 21 Peptides Identified from Library Based on "XXX OPY XXXX" with Peptide Competition Peptide YWY QPY ALGL YWY QPY ALPL EWI QPY ATGL NWE QPY AKPL AFY QPY ALPL FLY QPY ALPL VCK QPY LEWC To more clearly define the preferred sequences, several additional libraries were screened using a colony lift technique. In brief, cells were infected with phage encoding random peptides and were plated on media containing arabinose to induce expression of the random peptides. Colonies were transferred to nitrocellulose filters which were washed extensively and then incubated at 4°C with 33 P radiolabeled IL-IR. The filters were washed, dried, and exposed to X-ray film. The sequences of peptides identified using this technique are shown below. Table 22 Peptides Identified Using Colony Lift Procedure Peptide IC 50 ETPFTWEESNAYYWQPYALPL ++ QGWLTWQDSVDMYWQPYALPL N.D. FSEAGYTWPENTYWQPYALPL N.D. TESPGGLDWAKIYWQPYALPL N.D. DGYDRWRQSGERYWQPYALPL ++ TANVSSFEWTPGYWQPYALPL ++ Table 23 Peptides Identified from Library Based on "XXXXXXXXXXXX YWQPYALPL" Peptide IC 50 SVGEDHNFWTSE YWQPYALPL ++ MNDQTSEVSTFP YWQPYALPL N.D. SWSEAFEQPRNL YWQPYALPL N.D. QYAEPSALNDWG YWQPYALPL N.D. NGDWATADWSNY YWQPYALPL N.D. THDEHI YWQPYALPL N.D. MLEKTYTTWTPG YWQPYALPL N.D. WSDPLTRDADL YWQPYALPL N.D. SDAFTTQDSQAM YWQPYALPL N.D. GDDAAWRTDSLT YWQPYALPL N.D. AIIRQLYRWSEM YWQPYALPL N.D. ENTYSPNWADSM YWQPYALPL ++ MNDQTSEVSTFP YWQPYALPL N.D. SVGEDHNFWTSE YWQPYALPL N.D. QTPFTWEESNAY YWQPYALPL N.D. ENPFTWQESNAY YWQPYALPL N.D. VTPFTWEDSNVF YWQPYALPL N.D. QIPFTWEQSNAY YWQPYALPL N.D. QAPLTWQESAAY YWQPYALPL N.D. EPTFTWEESKAT YWQPYALPL N.D. TTTLTWEESNAY YWQPYALPL N.D. ESPLTWEESSAL YWQPYALPL N.D. ETPLTWEESNAY YWQPYALPL N.D. EATFTWAESNAY YWQPYALPL N.D. EALFTWKESTAY YWQPYALPL N.D. FTP-TWEESNAY YWQPYALPL N.D. ETPFTWEESNAY YWQPYALPL N.D. KAPFTWEESQAY YWQPYALPL N.D. STSFTWEESNAY YWQPYALPL N.D. DSTFTWEESNAY YWQPYALPL N.D. YIPFTWEESNAY YWQPYALPL N.D. QTAFTWEESNAY YWQPYALPL N.D. ETLFTWEESNAT YWQPYALPL N.D. VSSFTWEESNAY YWQPYALPL N.D. Analog analysis of the sequence N-terminal from the QPYALPL motif produced a peptide having the sequence pY(lNap)pYQJYALPL, having an IC 50 of less than 500 nM, where pY is phosphotyrosine and INap is naphthylalanine. Additionally, truncation of the peptide TANVSSFEWTPG YWQPYALPL yielded the peptide FEWTPGYWQPYALPL having an IC50 of less than 500 nM. Substitution of the proline in the QPY motif yielded a peptide of similar affinity, as did substitution of the tryptophan residue within the YW motif with tyrosine. These peptides are thus FEWTPGYWQJYALPL and FEWTPGYYQJYALPL. The peptide ETPFTWEESNAYYWQPYALPL was truncated at the N terminus, and the proline in the QPY motif was substituted with azetidine to yield the peptide FTWEESNAYYWQJYALPL, which had an IC 50 of less than 500 nM. Truncation of both the N-terminal ETP sequence and the C- terminal ALPL region in the original peptide, yielded the peptide FTWEESNAYYWQPY-NH 2 , having an IC 50 of less than 500 nM. Substitution of the proline in the QPY motif with azetidine, gives the peptide FTWEESNAYYWQJY-NH 2 , having a similarly strong affinity (an IC 50 of less than 500 nM) . Table 24 Other Peptides Identified by Colony Lifts with Labeled Receptor Peptide IC 50 ADVL YWQPYA PVTLWV N.D. GDVAE YWQPYA LPLTSL N.D. SWTDYG YWQPYA LPISGL ++ The above data illustrate a peptide comprising a core sequence of amino acids XXQZ 5 YZ 6 XX where X can be selected from any one of the 20 genetically coded L-amino acids; Z 5 is P or Aze where Aze is azetidine; and Z 6 is S, A, V, or L. More preferably, the sequence comprises Z 7 XQZ 5 YZ 6 XX where X can be selected from any one of the 20 genetically coded L-amino acids; Z 5 is P or Aze where Aze is azetidine; Z 6 is S or A; and Z 7 is Y, W, or F. In a more preferred embodiment, the core sequence of amino acids will comprise Z 7 Z 8 QZ 5 YZ 6 Z 9 Z 10 where Z 5 is P or Aze where Aze is azetidine; Z 6 is S or A; Z 7 is Y, W or F; Z 8 is E, F, V, W, or Y; Z 9 is M, F, V, R, Q, K, T, S, D, L, I, or E; and Z 10 is E, L, W, V, H, I, G, A, D, L, Y, N, Q or P. More preferably, Z 9 is V, L, I, or E; and Z 10 is Q or P. Most preferably, the core peptide will comprise a sequence of amino acids Z 11 Z 7 Z 8 QZ 5 YZ 6 Z 9 Z 10 , where Z 8 is Y, W or F; and Z lλ is V, L, I, E, P, G, Y, M, T, or, D. Specific examples of these peptides include FEWTPGYWQPYALPL, FEWTPGYWQJYALPL, FEWTPGWYQPYALPL, FEWTPGWYQJYALPL, FEWTPGYYQPYALPL and FEWTPGYYQJYALPL. An especially preferred embodiment is one having the substitution patterns just described, but comprising 21 amino acid residues. Particularly preferred is the peptide comprising the sequence of amino acids Z 12 Z 13 Z 14 Z 15 Z 16 Z 17 Z 18 Z 19 Z 20 Z 21 Z 22 Z 11 Z 7 Z 8Q Z 5 YZ 6 Z 9 Z 10 L ' w -h ere Z 8 ls Y, W or F; Z lλ is V, L, I, E, P, G, Y, M, T, or, D; Z 12 is A, D, E, F, G, K, Q, S, T, V, or Y; Z 13 is A, D, G, I, N, P, S, T, V, or W; Z 14 is A, D, G, L, N, P, S, T, W, or Y; Z 15 is A, D, E, F, L, N, R, V, or Y; Z 16 is A, D, E, Q, R, S, or T; Z 17 is H, I, L, P, S, T, or, W; Z 18 is A, E, F, K, N, Q, R, S, or Y; Z 19 is D, E, F, Q, R, T, or W; Z 20 is A, D, P, S, T, or W; Z 21 is A, D, G, K, N, Q, S, or T; and Z 22 is A, E, L, P, S, T, V, or Y. More preferably, Z 8 is Y, W or F; Z ι is V, L, I, E, P, G, Y, M, T, or, D; Z 12 is D, E, Q, S, T, V, or Y; Z 13 is A, D, G, I, N, S, T or V; Z 14 is A, G, L, N, P, S, T, or Y; Z 15 is D, E, F, L, V, or Y; Z 16 is D, R, S or T; Z 17 is H, P, S, or W; Z 18 is E, F, N, R, Q, or S; Z 19 is D, E, F, Q, or W; Z 20 is S, T, or W; Z 21 is D, G, K, N, Q, S, or T; and Z 22 is A, E, P, S, or Y. Particularly preferred peptides include TANVSSFEWTPGYWQPYALPL; SWTDYGYWQPYALPISGL; ETPFTWEESNAYYWQPYALPL; ENTYSPNWADSMYWQPYALPL; SVGEDHNFWTSEYWQPYALPL; and DGYDRWRQSGERYWQPYALPL. Truncations of the TANVSSFEWTPGYWQPYALPL peptide were synthesized and tested for their ability to inhibit the binding of IL-lα to IL-lRtI, and the following peptides were identified: Table 25 Peptide IC 50 FEWTPGYWQPYALPL ++ FEWTPGYWQPY-NH 2 ++ FEWTPGYWQJY-NH2 ++ EWTPGYWQPY-NH 2 + FEWTPGWYQJY-NH 2 ++ Deletion of the six N-terminal amino acids was found to have little effect on the affinity of the peptide. While deletion of the C-terminal ALPL sequence resulted in a five¬ fold decrease, the llmer peptide was still found to be a good inhibitor of IL-lα binding, having an IC 50 of well below 500 nM. Furthermore, substitution of azetidine (J) for the proline in the number 10 position of the llmer restored much of the lost affinity. Deletion of the N-terminal phenylalanine, however, resulted in a large reduction in affinity. The llmer, FEWTPGYWQJY-NH 2 , was subject to further substitution and analoging. Specifically, sequential alanine substitution was used to determine the important functional positions in the sequence of the peptide. The following peptides and results were obtained from the alanine substitution: Table 26 Peptide IC 50 AEWTPGYWQJY-NH 2 + FAWTPGYWQJY-NH 2 ++ FEATPGYWQJY-NH 2 + FEWAPGYWQJY-NH 2 ++ FEWTAGYWQJY-NH 2 ++ FEWTPAYWQJY-NH 2 ++ FEWTPGAWQJY-NH 2 +/++ FEWTPGYAQJY-NH 2 + FEWTPGYWAJY-NH 2 FEWTPGYWQJA-NH 2 + Alanine substitution at positions 2 and 4 yielded no appreciable loss in affinity of the peptide. These data therefore indicate that the residue requirements in these positions are flexible. Alanine substitutions at positions 5, 6 and 7, while somewhat affecting affinity, still yielded peptides with strong affinity. These positions are therefore considered moderately flexible as to their specific amino acid requirements. Table 27 Substitution and Analoging the PG Motif Peptide IC 50 FEWTGGYWQJY-NH 2 + FEWTpGYWQJY-NH 2 ++ FEWTJGYWQJY-NH 2 ++ FEWTPecGYWQJY-NH 2 ++ FEWTPAibYWQJY-NH 2 ++ FEWTPSarWYQJY-NH 2 ++ FEWTSarGYWQJY-NH 2 ++ FEWTPNYWQJY-NH 2 ++ FEWTPvYWQJY-NH 2 ++ FEWTVPYWQJY-NH 2 + AcFEWTPGWYQJY-NH 2 ++ AcFEWTPGYWQJY-NH 2 ++ Acetylation of the N-terminal phenylalanine was found to have little impact on affinity. Further analoguing of the lead peptide yielded the active peptides shown in the table, below. Table 28 Additional Analoging of 11-mer Peptides Peptide IC 50 (Me 3 N) INap-EWTPaWYQJY ++ AcFEWTPaWYQJY ++ FEWTPnYYQJY ++ AcFEWTPGYYQJY ++ (Me 3 N) F-EWTPGWYQJY ++ AcFEWTPaYYQJY ++ Ac2Nap-EWTPaYWQJY ++ (Me 3 N) 2Nap-EWTPaWYQJY ++ FEWTPGWYQJY ++ AcWEWTPaYWQJY ++ AcY(0CH 3 ) -EWTPaYWQJY ++ AcF(4-N0 2 ) -EWTPaYWQJY ++ (Me 2 N) F-EWTPaWYQJY ++ (Me 2 N) F-EWTPaWYQJY ++ AcYEWTPaYWQJY ++ (Me 3 N)Bta-EWTPaWYQJY ++ AcFEWTPaWYQJY ++ (Me 3 N)F-EWTPaQJY ++ AcFEWTPaFWQJY ++ HO-(R)-F-EWTPGWYQJY ++ (Me 3 N) 2Nap-EWTPaWY-(NMe)Q-JY ++ FEW-Nle-PGYWQJY ++ AcFEWTPdWYQJY ++ AcFEWTPaY-(4NH 2 ) F-QJY ++ FEW-alloThr-PGYWQJY ++ AcFEWTPa-(4-N0 2 )F-WQJY ++ AcFEWTPkWYQJY ++ AcFEWTPa-(4-NH 2 )F-YQJY ++ Ac-FQWTPaYWQJY ++ (Me 3 N)Tha-EWTPaWYQJY ++ AcPya-EWTPaYWQJY ++ AcFEWTPa-(4-NH 2 )F-WQJY ++ NH 2 (=0)F-EWTPaYWQJY ++ Ac-Thc-EWTPaYWQJY ++ AcFEWTPa-Y(OCH 3 ) -WYQJY ++ HO-(S) -F-EWTPGWYQJY ++ AcF-E(OCH 3 )-WTPaYWQJY ++ ACFEWTPaYWQJF ++ AcFEWTPaY-(4-N0 2 ) F-QJY ++ AcFEWTPaW-Y(OCH 3 ) -QJY ++ ACFEWTP-(NMe-a) -WYQJY ++ AcFEWTPaYWQJ-(4-NH 2 ) F ++ FEWTJGYWQJY ++ AcFMWTPaYWQJY ++ AcFDWTPaYWQJY ++ AcFEWTPa-Y(OCH 3 ) -YQJY ++ AcFEWT-(NMe-A) -aWYQJY ++ AcFEWTPfWYQJY ++ AcFEWTPaY-Pya-QJY ++ AcFHWTPaYWQJY ++ AcFEWIPaYWQJY ++ ACfEWTPaYWQJY ++ FEWSPGYWQJY ++ FEWTAGYWQJY +-•- FEWTpGYWQJY ++ ACHEWTPaYWQJY ++ Ac-hmoF-EWTPaYWQJY ++ AcFEWAPpYWQJY ++ AcFEW-Nle-PaYWQJY ++ AcFEYTpaYWQJY ++ AcFEWTPa-Thc-YQJY ++ AcFE-(4-N0 2 ) F-TPaYWQJY + des(NH 2 ) F-EWTPaWYQJY + FE-lNap-TPGWYQJY + AcFEFTPaYWQJY + AcFEWTPaYWQJY-Y(OCH 3 ) + AcFEWTPaY-Thc-QJY + AcFEWTPaWYQJ-Pya + Ac-Tiq-EWTPaWYQJY + Ac-Cha-EWTPaWYQJY + AcFE-Pya-TPaYWQJY + AcPhg-EWTPaYWQJY + AcFEWTPaWYQJ(4-N0 2 ) F + AcFE-Thc-TPaYWQJY + Combinatorial libraries were prepared using both the ESL and VLSIPS™ methods, based upon the general peptide sequence XXXXPGYYQJY, where the X residues are substituted with a number of different building blocks. A number of peptides were identified as having apparent strong affinity, and these peptides were synthesized, and their binding affinities determined. The results are summarized below. Table 29 Combinatorial Library Based upon XXXXPGYYQJY Peptide IC 50 lNap-EWTPGYYQJY-NH 2 ++ YEWTPGYYQJY-NH 2 ++ FEWVPGYYQJY-NH 2 ++ A similar combinatorial strategy focused upon the central PG motif of the FEWTPGYYQJY peptide. The peptides FEWTPsYYQJY-NH 2 and FEWTPnYYQJY-NH 2 were identified as having IC 50 s well below 500 nM. The preferred motif sequences also provide a means to determine the minimum size of an IL-IR blocking compound of the invention. One may use the "encoded synthetic library" (ESL) system described in U.S. patent application Serial No. 946,239, filed September 16, 1992, which is a continuation-in-part application of Serial No. 762,522, filed September 18, 1991, or the "very large scale immobilized polymer synthesis" system described in U.S. patent application Serial Nos. 492,462, filed March 7, 1990; 624,120, filed December 6, 1990; and 805,727, filed December 6, 1991; to not only determine the minimum size of a peptide with such activity, one can also make all of the peptides that form the group of peptides that differ from the preferred motif (or the minimum size of that motif) in one, two, or more residues. This collection of peptides can then be screened for ability to bind to IL-1-receptor. This immobilized polymer synthesis system or other peptide synthesis methods can also be used to synthesize every truncation analog and every deletion analog and every combination of truncation and deletion analog of all of the peptide compounds of the invention. The peptides of the invention can be prepared by classical methods known in the art, for example, by using standard solid phase techniques. The standard methods include exclusive solid phase synthesis, partial solid phase synthesis methods, fragment condensation, classical solution synthesis, and even by recombinant DNA technology. See, e.g., Merrifield (1963) J . Am . Chem . Soc . 85:2149, incorporated herein by reference. On solid phase, the synthesis is typically commenced from the C-terminal end of the peptide using an alpha-amino protected resin. A suitable starting material can be prepared, for instance, by attaching the required alpha-amino acid to a chloromethylated resin, a hydroxymethyl resin, or a benzhydrylamine resin. One such chloromethylated resin is sold under the trade name BIO-BEADS SX-1 by Bio Rad Laboratories, Richmond, CA, and the preparation of the hydroxymethyl resin is described by Bodanszky et al ., (1966) Chem . Ind . (London) 38:1597. The benzhydrylamine (BHA) resin has been described by Pietta and Marshall (1970) Chem . Commn . 650, and is commercially available from Beckman Instruments, Inc., Palo Alto, CA, in the hydrochloride form. Thus, the compounds of the invention can be prepared by coupling an alpha-amino protected amino acid to the chloromethylated resin with the aid of, for example, cesium bicarbonate catalyst, according to the method described by Gisin (1973) Helv . Chim . Acta 56:1467. After the initial coupling, the alpha-amino protecting group is removed by a choice of reagents including trifluoroacetic acid (TFA) or hydrochloric acid (HCl) solutions in organic solvents at room temperature. The alpha-amino protecting groups are those known to be useful in the art of stepwise synthesis of peptides. Included are acyl type protecting groups (e.g., formyl, trifluoroacetyl, acetyl) , aromatic urethane type protecting groups (e.g., benzyloxycarboyl (Cbz) and substituted Cbz) , aliphatic urethane protecting groups (e.g., t-butyloxycarbonyl (Boc) , isopropyloxycarbonyl, cyclohexyloxycarbonyl) and alkyl type protecting groups (e.g., benzyl, triphenylmethyl) . Boc and Fmoc are preferred protecting groups. The side chain protecting group remains intact during coupling and is not split off during the deprotection of the amino-terminus protecting group or during coupling. The side chain protecting group must be removable upon the completion of the synthesis of the final peptide and under reaction conditions that will not alter the target peptide. The side chain protecting groups for Tyr include tetrahydropyranyl, tert-butyl, trityl, benzyl, Cbz, Z-Br-Cbz, and 2,5-dichlorobenzyl. The side chain protecting groups for Asp include benzyl, 2 , 6-dichlorobenzyl, methyl, ethyl, and cyclohexyl. The side chain protecting groups for Thr and Ser include acetyl, benzoyl, trityl, tetrahydropyranyl, benzyl, tert-butyl 2,6-dichlorobenzyl, and Cbz. The side chain protecting groups for Arg include nitro, Tosyl (Tos) , Cbz, adamantyloxycarbonyl mesitoylsulfonyl (Mts) , or Boc. The side chain protecting groups for Lys include Cbz, 2-chlorobenzyloxycarbonyl (2-Cl-Cbz) , 2-bromobenzyloxycarbonyl (2-BrCbz) , Tos, or Boc. After removal of the alpha-amino protecting group, the remaining protected amino acids are coupled stepwise in the desired order. An excess of each protected amino acid is generally used with an appropriate carboxyl group activator such as dicyclohexylcarbodiimide (DCC) in solution, for example, in methylene chloride (CH 2 C1 2 ) , dimethyl formamide (DMF) mixtures. After the desired amino acid sequence has been completed, the desired peptide is decoupled from the resin support by treatment with a reagent such as trifluoroacetic acid or hydrogen fluoride (HF) , which not only cleaves the peptide from the resin, but also cleaves all remaining side chain protecting groups. When the chloromethylated resin is used, hydrogen fluoride treatment results in the formation of the free peptide acids. When the benzhydrylamine resin is used, hydrogen fluoride treatment results directly in the free peptide amide. Alternatively, when the chloromethylated resin is employed, the side chain protected peptide can be decoupled by treatment of the peptide resin with ammonia to give the desired side chain protected amide or with an alkylamine to give a side chain protected alkylamide or dialkylamide. Side chain protection is then removed in the usual fashion by treatment with hydrogen fluoride to give the free amides, alkylamides, or dialkylamides. In preparing the compounds of the invention, the resins used to prepare the peptide acids are employed, and the side chain protected peptide is cleaved with base and the appropriate alcohol, i.e., methanol. Side chain protecting groups are then removed in the usual fashion by treatment with hydrogen fluoride to obtain the desired ester. These solid phase peptide synthesis procedures are well known in the art and further described in Stewart, Solid Phase Peptide Syntheses (Freeman and Co., San Francisco, 1969). These procedures can also be used to synthesize peptides in which amino acids other than the 20 naturally occurring, genetically encoded amino acids are substituted at one, two, or more positions of any of the compounds of the invention. For instance, naphthylalanine can be substituted for tryptophan, facilitating synthesis. Other synthetic amino acids that can be substituted into the peptides of the present invention include L-hydroxypropyl, L-3, 4-dihydroxyphenylalanyl, α amino acids such as L-α-hydroxylysyl and D-α-methylalanyl, L-α-methylalanyl, β amino acids, and isoquinolyl. D amino acids and non-naturally occurring synthetic amino acids can also be incorporated into the peptides of the present invention. One can replace the naturally occurring side chains of the 20 genetically encoded amino acids (or D amino acids) with other side chains, for instance with groups such as alkyl, lower alkyl, cyclic 4-, 5-, 6-, to 7-membered alkyl, amide, amide lower alkyl, amide di(lower alkyl) , lower alkoxy, hydroxy, carboxy and the lower ester derivatives thereof, and with 4-, 5-, 6-, to 7-membered heterocyclic. In particular, proline analogs in which the ring size of the proline residue is changed from 5 members to 4, 6, or 7 members can be employed. Cyclic groups can be saturated or unsaturated, and if unsaturated, can be aromatic or non-aromatic. For example, the following peptides were prepared where "Nap" represents naphthylalanine and "J" or "Aze" represents azetidine. Table 30 Peptide IC 50 SHLY-Nap-QPYSVQM + TLVY-Nap-QPYSLQT + RGDY-Nap-QPYSVQS + NMVY-Nap-QPYSIQT + VYWQPYSVQ + VY-Nap-QPYSVQ + TFVYWQJYALPL + The peptides of the present invention may also have incorporated within their sequence, a photoreactive amino acid. For example, p-benzoyl-L-phenylalanine may be readily incorporated into the amino acid sequence of the peptides described herein. This amino acid derivative is photolyzed by exposure to electromagnetic radiation at or near the UV range of the spectrum, e.g., 350 nm. When photolyzed, this amino acid analog attacks proximal C-H bonds, resulting in the formation of a covalent complex. See, e.g., Dorman, et al., Biochemistry 33:5661-5673 (1994) . By varying the position of the Bpa residue within the peptide sequence, the peptides may be used as photolabels to map the IL-1 binding domain, and more particularly, to determine the specific residues which interact with the ligand binding domain of the IL-1 receptor. See, Kauer, et al., J. Biol. Chem. 261(23) : 10695-10700 (1986) . Determination of which peptides form a covalent complex may be carried out by standard HPLC methods, e.g., as described in Kauer, et al., or optionally, the peptide may comprise any of a number of labelling groups to facilitate detection. The following specific peptides were prepared by substituting various positions of the peptide AcFEWTPGYYQJY- NH 2 , having both free and acetylated N-terminals, with p- benzoyl-L-phenylalanine ("Bpa") . The resulting peptides and their approximate binding affinities are listed below: Table 31 Photoreactive Peptides Peptide IC 50 FEWTPGYYQJ-Bpa-NH 2 + AcFEWTPGYYQJ-Bpa-NH 2 + FEWTPGY-Bpa-QJY-NH 2 ++ AcFEWTPGY-Bpa-QJY-NH 2 ++ FEWTPG-Bpa-YQJY-NH 2 ++ AcFEWTPG-Bpa-YQJY-NH 2 ++ FE-Bpa-TPGYYQJY-NH 2 AcFE-Bpa-TPGYYQJY-NH 2 + Bpa-EWTPGYYQJY-NH 2 ++ AcBpa-EWTPGYYQJY-NH 2 ++ From the above tables, preferred high affinity peptides were identified which comprise an 11 amino acid core sequence z 3 iX z 4 i z 32 z 3 3 z 34 z 35 z 36 z 42 z 37 z 38 ' including amides and esters thereof. In this core sequence, each letter represents the standard one letter abbreviation for an amino acid or an analog thereof. The residue represented by X may be any natural or unnatural amino acid. The residue in position Z 31 may generally be phenylalanine, tyrosine, 1-naphthylalanine, 2- naphthylalanine, p-benzoyl-L-phenylalanine, tryptophan, histidine, homophenylalanine, 3-pyridylalanine, thienylalanine, benzothienylalanine, cyclohexylalanine, phenylglycine, D-phenylalanine, , tetrahydroisoquinoline, tetrahydro-jS-carboline, D and L-DES-aminophenylalanine. As can be seen, alkylated or arylated alanine residues are readily substituted for the phenylalanine residue at the Z 31 position. The Z 32 residue may be any natural or unnatural amino acid, however, alanine, threonine, allothreonine, isoleucine, norleucine, serine and valine are preferred. Z 33 may be selected from proline, D-proline, alanine, glycine, N-methylalanine, azetidine, sarcosine and pipecolic acid. Z 34 may be selected from glycine, asparagine, any D- amino acid, sarcosine, and aminoisobutyric acid, represented by Sar and Aib, respectively. The Z 35 residue may be a natural or unnatural amino acid, and is preferably selected from tyrosine, phosphotyrosine (denoted n -pY-") , phenylalanine, tryptophan, 1-naphthylalanine and p-benzoyl-L-phenylalanine, 4- nitrophenylalanine, 4-aminophenylalanine, 4- ethoxyphenylalanine and tetrahydro-β-carboline. Z 36 is preferably selected from from tyrosine, phosphotyrosine (denoted "-pY-") , phenylalanine, tryptophan, 1-naphthylalanine and p-benzoyl-L-phenylalanine, 4- nitrophenylalanine (4-N02-Phe) , 4-aminophenylalanine (4-NH 2 - Phe) , 4-methoxyphenylalanine (4-CH30-Phe) and tetrahydro-j8- carboline and 3-pyridylalanine. The Z 37 residue can be any natural or unnatural cyclic amino acid, with proline and azetidine being preferred. The residue at position Z 38 is selected from tyrosine tyrosinamide and substituted tyrosinamide. Z 41 is selected from tryptophan, 4- nitrophenylalanine, 4-aminophenylalanine, 4- methoxyphenylalanine, and tetrahydro-/3-carboline with tryptophan, phenylalanine, '4-nitrophenylalanine and 1- naphthylalanine being preferred. Z 42 is selected from glutamine and N-methylglutamine with glutamine being preferred. Particularly preferred peptides include those having the following core sequences: FEWTPGYWQPY-NH 2 ; FEWTPGYWQJY- NH 2 ; FEWTPGWYQJY-NH 2 ; AcFEWTPGWYQJY-NH 2 ; FEWTPGW-pY-QJY-NH 2 ; FAWTPGYWQJY-NH 2 ; FEWAPGYWQJY-NH 2 ; FEWVPGYWQJY-NH 2 ; FEWTPGYWQJY-NH 2 ; AcFEWTPGYWQJY-NH 2 ; FEWTPaWYQJY-NH 2 ; FEWTP- Sar-WYQJY-NH 2 ; FEWTPGYYQPY-NH 2 ; FEWTPGWWQPY-NH 2 ; FEWTPNYWQPY- NH 2 ; FEWTPvYWQJY-NH 2 ; and FEWTPGYWQPYALPL; FEWTPGYYQJ-Bpa-NH 2 ; AcFEWTPGYYQJ-Bpa-NH 2 ; FEWTPGY-Bpa-QJY-NH 2 ; AcFEWTPGY-Bpa-QJY- NH 2 ; FEWTPG-Bpa-YQJY-NH 2 ; AcFEWTPG-Bpa-YQJY-NH 2 ; FE-Bpa- TPGYYQJY-NH 2 ; AcFE-Bpa-TPGYYQJY-NH 2 ; Bpa-EWTPGYYQJY-NH 2 ; AcBpa-EWTPGYYQJY-NH 2 ; lNap-EWTPGYYQJY-NH 2 ; YEWTPGYYQJY-NH 2 ; FEWVPGYYQJY-NH 2 ; (Me 3 N) INap-EWTPaWYQJY; AcFEWTPaWYQJY; FEWTPnYYQJY; AcFEWTPGYYQJY, (Me 3 N)F-EWTPGWYQJY, AcFEWTPaYYQJY; Ac2Nap-EWTPaYWQJY; (Me 3 N) 2Nap-EWTPaWYQJY; FEWTPGWYQJY; AcWEWTPaYWQJY; AcY(OCH 3 ) -EWTPaYWQJY; AcF(4-N0 2 ) -EWTPaYWQJY; (Me 2 N) F-EWTPaWYQJY; (Me 2 N)F-EWTPaWYQJY; AcYEWTPaYWQJY; (Me 3 N)Bta-EWTPaWYQJY; AcFEWTPaWYQJY; (Me 3 N)F- EWTPaQJY; AcFEWTPaFWQJY; HO-(R) -F-EWTPGWYQJY; (Me 3 N) 2Nap-EWTPaWY-(NMe)Q-JY; FEW-Nle-PGYWQJY; AcFEWTPdWYQJY; AcFEWTPaY-(4NH 2 ) F-QJY; FEW-alloThr-PGYWQJY; AcFEWTPa-(4-N0 2 ) F-WQJY; AcFEWTPkWYQJY; AcFEWTPa-(4-NH 2 )F-YQJY; Ac-FQWTPaYWQJY; (Me 3 N)Tha-EWTPaWYQJY; AcPya-EWTPaYWQJY; AcFEWTPa-(4-NH 2 )F-WQJY; NH 2 (=0)F-EWTPaYWQJY; Ac-Thc- EWTPaYWQJY; AcFEWTPa-Y(OCH 3 ) -WYQJY; HO-(S) -F-EWTPGWYQJY; AcF- E(OCH 3 )-WTPaYWQJY; ACFEWTPaYWQJF; AcFEWTPaY-(4-N0 2 )F-QJY; AcFEWTPaW-Y(OCH 3 ) -QJY; ACFEWTP-(NMe-a) -WYQJY; AcFEWTPaYWQJ-(4-NH 2 )F; FEWTJGYWQJY; AcFMWTPaYWQJY; AcFDWTPaYWQJY; AcFEWTPa-Y(OCH 3 ) -YQJY; AcFEWT-(NMe-A) -aWYQJY; AcFEWTPfWYQJY; AcFEWTPaY-Pya-QJY; AcFHWTPaYWQJY; AcFEWIPaYWQJY; ACfEWTPaYWQJY; FEWSPGYWQJY; FEWTAGYWQJY; FEWTpGYWQJY; ACHEWTPaYWQJY; Ac-hmoF-EWTPaYWQJY; AcFEWAPpYWQJY; AcFEW-Nle-PaYWQJY; AcFEYTpaYWQJY; AcFEWTPa-Thc-YQJY; AcFE-(4- N0 2 )F-TPaYWQJY; des(NH 2 ) F-EWTPaWYQJY; FE-lNap-TPGWYQJY; AcFEFTPaYWQJY; AcFEWTPaYWQJY-Y(OCH 3 ) ; AcFEWTPaY-Thc-QJY; AcFEWTPaWYQJ-Pya; Ac-Tiq-EWTPaWYQJY; Ac-Cha-EWTPaWYQJY; and AcFE-Pya-TPaYWQJY. Although shown as free amino and carboxy terminals, peptides comprising substituted amino termini and amidated carboxy groups are also included. For example, in addition to acetylated N-termini, the amine group can also be substituted, acylated or alkylated with 2-3 substituent groups resulting in a tertiary or quaternary amine. Such analogs continue to retain high affinity. Examples of such tertiary or quaternary amines include, e.g., 4-chlorophenylalanine, 4- methoxyphenylalanine (CH 3 0-) 4 , 4-nitrophenylalanine (N0 2 -) 4 , 4-aminophenylalanine (NH 2 0) 4 , and the like. Other preferred peptides of the invention synthesized by techniques standard in the art are shown below. Table 32 Peptide VYWQPYSVQ RLVYWQPYSVQR RLVY-Nap-QPYSVQR RLDYWQPYSVQR RLVWFQPYSVQR RLVYWQPYSIQR B.Non QPY llmer Peptides Another sequence motif was identified by screening a pVIII 11-mer library. This sequence comprises Z 23 NZ 24 Z 39 Z 25 Z 26 Z 2 7 Z 28 Z 2 9 Z 30 Z 40 where Z 23 is D or Y; Z 24 is D, S or T; Z 39 is S, T or A; Z 25 is S or W; Z 26 is S or Y; Z 27 is D, Q, E or V; Z 28 is N, S, K, H or W; Z 29 is F or L; Z 30 is D, N, S or L; and Z 40 is L, I, Q, M or A. Representative samples of this sequence motif include: Table 33 Peptide ISso DNSSWYDSFLL + DNTAWYESFLA + DNTAWYENFLL + Two extension libraries were prepared based upon the peptide XXXXDNTAWYESFLLXX, where X residues were encoded using NNK, the underlined residues were mutagenized using the 70-10- 10-10 approach, and the remaining residues were kept fixed. Probing with bivalent 33 P-labelled receptor identified the following clones: Table 34 Peptide PARE DNTAWYDSFLI WC TSEY DNTTWYEKFLA SQ SQIP DNTAWYQSFLL HG SPFI DNTAWYENFLL TY EQIY DNTAWYDHFLL SY TPFI DNTAWYENFLL TY TYTY DNTAWYERFLM SY TMTQ DNTAWYENFLL SY The peptide TYTYDNTAWYERFLMSY was assayed for affinity and yielded an IC 50 well below 500 nM. The second, similar library was prepared switching the length of the amino and carboxy-terminal extensions. Thus the library was based upon the peptide XXDNTAWYESFLLXXXX. The following sequences were identified: Table 35 Peptide TI DNTAWYANLVQ TYPQ TI DNTAWYERFLA QYPD HI DNTAWYENFLL TYTP SQ DNTAWYENFLL SYKA QI DNTAWYERFLL QYNA NQ DNTAWYESFLL QYNT TI DNTAWYENFLL NHNL HY DNTAWYERFLQ QGWH The peptides HIDNTAWYENFLLTYTP and QIDNTAWYERFLLQYNA were assayed for affinity and yielded an IC 50 well below 500 nM. The present invention also includes the peptides of the invention which have been modified, including, e.g., truncations, deletions, analogs, acylated and/or amidated derivatives, and the like. For example, the peptides may be truncated at either the amino or carboxy terminus, or both. Additionally, although the peptides have been described in terms of having a free carboxy and/or amino termini, it may also be appreciated that one can modify the amino and/or carboxy terminus of the peptide compounds of the invention to produce other compounds of the invention. For example, amino terminus modifications/substitutions include methylating (i.e., -NHCH 3 , -NH(CH 3 ) 2 , -NCH 3 ) , acylating, acetylating, adding a benzyloxycarbonyl group, halogenating, or blocking the amino terminus with any blocking group containing a carboxylate functionality defined by RCOO-, where R is selected from the group consisting of naphthyl, acridinyl, steroidyl, and similar groups. Carboxy terminus modifications include replacing the free acid with a carboxamide group or forming a cyclic lactam at the carboxy terminus to introduce structural constraints. One can also cyclize the peptides of the invention, or incorporate a desamino or descarboxy residue at the termini of the peptide, so that there is no terminal amino or carboxy1 group, to decrease susceptibility to proteases or to restrict the conformation of the peptide. C-terminal functional groups of the compounds of the present invention include amide, amide lower alkyl, amide di(lower alkyl), lower alkoxy, hydroxy, and carboxy, and the lower ester derivatives thereof, and the pharmaceutically acceptable salts thereof. One can also readily modify peptides by phosphorylation, and other methods for making peptide derivatives of the compounds of the present invention are described in Hruby et al . , (1990) Biochem J. 268(2) :249-262, incorporated herein by reference. Thus, the peptide compounds of the invention also serve as structural models for non-peptidic compounds with similar biological activity. Those of skill in the art recognize that a variety of techniques are available for constructing compounds with the same or similar desired biological activity as the lead peptide compound but with more favorable activity than the lead with respect to solubility, stability, and susceptibility to hydrolysis and proteolysis. See Morgan and Gainor (1989) Ann. Rep. Med . Chem . 24:243-252, incorporated herein by reference. These techniques include replacing the peptide backbone with a backbone composed of phosphonates, amidates, carbamates, sulfonamides, secondary amines, and N-methylamino acids. IV. In Vitro Uses The compounds of the invention are useful in vitro as unique tools for understanding the biological role of IL-1, including the evaluation of the many factors thought to influence, and be influenced by, the production of IL-1 and the receptor binding process. The present compounds are also useful in the development of other compounds that bind to the IL-lRtI, because the present compounds provide important information on the relationship between structure and activity that should facilitate such development. The compounds are also useful as competitive inhibitors in assays to screen for new IL-1 receptor blockers. Specifically, the present invention includes peptides which bind the IL-lRtI, and wherein that binding is competitively inhibited by other peptides of the invention, e.g., those having the core sequences described herein. In such assay embodiments, the compounds of the invention can be used without modification or can be modified in a variety of ways; for example, by labeling, such as covalently or non-covalently joining a moiety which directly or indirectly provides a detectable signal. In any of these assays, the materials thereto can be labeled either directly or indirectly. Possibilities for direct labeling include label groups such as: radiolabels such as 125 I, enzymes (US Patent 3,645,090) such as peroxidase and alkaline phosphatase, and fluorescent labels (US Patent 3,940,475) capable of monitoring the change in fluorescence intensity, wavelength shift, or fluorescence polarization. Possibilities for indirect labeling include biotinylation of one constituent followed by binding to avidin coupled to one of the above label groups. The compounds may also include spacers or linkers in cases where the compounds are to be attached to a solid support. Methods of determining whether a compound competitively inhibits IL-1 receptor binding of a peptide of the invention are well known in the art. See, e.g. Stryer, Biochemistry, W.H Freeman and Co. (1988) . Additionally, the peptides of the present invention may be used to label, and thereby ascertain and study the nature of the IL-lRtI/ligand interaction. In particular, those peptides which comprise p-benzoyl-L-phenylalanine derivatives within their sequence may be used to photolabel particular residues within the IL-lRtI sequence which are involved in the interaction and/or binding of the receptor's ligand. See, e.g., Kauer, et al., J.Biol. Chem. (1986) 261(23) :10695-10700. The compounds of the invention can also be used in assays as probes for determining the expression of the IL-lRtI on the surface of cells. Such an assay is useful for determining the degree of cellular immunological and inflammatory response, for example to infection and tissue injury. Typically, the cells under study will be exposed to the compounds for a period sufficient for the compounds to bind to the receptor(s) exposed on the cell surface. The cells are then separated from the non-bound compounds and unreacted cells, e . g. , by affinity chromatography or the use of a cell sorter, to identify whether binding of the compounds to the receptor has occurred. Thus, the compositions and methods of the present invention also can be used in vitro for testing a patient's susceptibility to varying treatment regimens for disorders associated with the overproduction of IL-1 or an improper response to IL-1 using an in vitro diagnostic method whereby a specimen is taken from the patient and is treated with a IL-lRtI binding, IL-1 blocking compound of the present invention to determine the effectiveness and amount of the compound necessary to produce the desired effect. The blocking compound and dosage can be varied. After the blocking compounds are screened, then the appropriate treatment and dosage can be selected by the physician and administered to the patient based upon the results. Therefore, this invention also contemplates use of a blocking compound of this invention in a variety of diagnostic kits and assay methods. V. In Vivo Uses The compounds of the invention can also be administered to warm blooded animals, including humans, to block the binding of IL-lα or IL-1/3 to the IL-lRtI in vivo . Thus, the present invention encompasses methods for therapeutic treatment of IL-1 related disorders that comprise administering a compound of the invention in amounts sufficient to block or inhibit the binding of IL-1 to the IL-IR in vivo . For example, the peptides and compounds of the invention can be administered to treat symptoms related to the overproduction of IL-1 or an improper response to IL-1. Since the biological effects of IL-1 include immunologic properties, such as T-cell activation, increased IL-2R expression, B-cell activation via induction of IL-6, natural killer cell activity, and lymphokine gene expression; pro-inflammatory properties such as fever, sleep, anorexia, neuropeptide release, gene expression for complement, suppression of P450 synthesis, endothelial cell activation, neutrophilia, increased adhesion molecule expression, neutrophil priming, eosinophil degranulation, hypotension, myocardial suppression, neutrophil tissue infiltration, beta islet cell cytotoxicity, hyperlipidemia, cyclooxygenase and lipoxygenase gene expression, synthesis of collagenases and collagens, and osteoblast activation, the compositions and methods described herein will find use for the treatment and/or prevention of a variety of IL-1 related disorders. See, e . g . , Dinarello (1991) Blood 8:1627-1652, which is incorporated herein by reference. Examples of specific disorders having such symptoms include but are not limited to, atherlerosclerosis, rheumatoid arthritis, osteoporosis, HIV infection and AIDS, bacterial infection, respiratory distress syndrome, acute myelogenous leukemia ("AML") , graft vs. host disease, coal miner pneumonoconiosis, alcoholic cirrhosis, cuprophane hemodialysis, cardiopulmonary bypass, chronic hepatitis B, thermal injury, reticulohistiocytosis, sarcoidosis, tuberculosis, obstructive jaundice, Paget's disease and osteomalacia, IDDM, Kawasaki's disease, inflammatory bowel disease, sepsis, toxic shock, and luteal phase. Accordingly, the present invention includes pharmaceutical compositions comprising, as an active ingredient, at least one of the peptides or other compounds of the invention in association with a pharmaceutical carrier or diluent. The compounds of this invention can be administered by oral, parental (intramuscular, intraperitoneal, intravenous (IV) or subcutaneous injection) , nasal, vaginal, rectal, or sublingual routes of administration and can be formulated in dosage forms appropriate for each route of administration. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert pharmaceutically acceptable carrier such as sucrose, lactose, or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, with the elixirs containing inert diluents commonly used in the art, such as water. Besides such inert diluents, compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents. Preparations according to this invention for parental administration include sterile aqueous or non-aqueous solutions, suspensions, or emulsions. Examples of non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and corn oil, gelatin, and injectable organic esters such as ethyl oleate. Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents. They may be sterilized by, for example, filtration through a bacteria retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured using sterile water, or some other sterile injectable medium, immediately before use. Compositions for rectal or vaginal administration are preferably suppositories which may contain, in addition to the active substance, excipients such as cocoa butter or a suppository wax. Compositions for nasal or sublingual administration are also prepared with standard excipients well known in the art. The quantities of the IL-1 blocking compound necessary for effective therapy will depend upon many different factors, including means of administration, target site, physiological state of the patient, and other medicants administered. Thus, treatment dosages should be titrated to optimize safety and efficacy. Typically, dosages used in vitro may provide useful guidance in the amounts useful for in situ administration of these reagents. Animal testing of effective doses for treatment of particular disorders will provide further predictive indication of human dosage. Various considerations are described, e.g., in Gilman et al. (eds), (1990) Goodman and Gilman ' s : The Pharmacological Basis of Therapeutics , 8th ed. , Pergamon Press; and Remington ' s Pharmaceutical Sciences , (1985) 7th ed. , Mack Publishing Co., Easton, Penn. ; each of which is hereby incorporated by reference. The dosage of active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient shall be such that a suitable dosage form is obtained. For the IL-1 blocking compounds of the invention exhibiting high affinity binding with IL-1 receptor, low dosages would be initially expected to be effective. Thus, generally dosage levels of between about 0.001 and 10 mg/kg, preferably between about 0.01 to 10 mg/kg, and more preferably between about 0.1 and 10 mg/kg of body weight daily will be administered to mammals to obtain effective IL-1 blocking activity. It should, of course, be understood that the compositions and methods of this invention can be used in combination with other agents exhibiting the ability to modulate IL-1 synthesis, release, and/or binding. Examples of such agents include, but are not limited to disease modifying antirheumatic drugs chloroquine, auranofin, sodium aurothiomalate, and dexamethasone (see, e.g., Lee et al . (1988) Proc . Natl . Acad . Sci . 85:1204); tenidap (see, e.g., Otterness, 3rd Interscience World Conference on Inflammation, Monte-Carlo, Abstr. p. 371 (March, 1989) ; antioxidants, such as nordihydroguaiaretic acid (see, e.g., Lee et al . (1988) Jnt. J. Immunopharmacol . 10:835), probucol (see, e . g. , Ku et al . (1988) Am . J . Cardiol . 62:778) , and disulfiram (see, e . g . , Marx (1988) Science 239:257) ; pentoxifylline (see, e.g., Sullivan et al . (1988) Infect . Immun . 56:1722) ; denbufylline (see, e.g., Mandell et al . PCT publication WO 89/015145 (1989); romazarit (see, e.g., Machin et al . (1988) U.S. Patent No. 4,774,253); tiaprofenic acid; dexamethasone; and natural macromolecular IL-1 inhibitors (see, e.g., Rosenstreich et al . in "Lymphokineε", E. Pick, Ed., 14:6 Academic Press (1987) and Larrick (1989) Immunol. Today 10:6); as well as the other agents described in Bender and Lee (1989) Annual Reports in Medicinal Chemistry Chapter 20 : Pharmacological Modulation of Interleukin-1 , pp. 185-193, which is incorporated herein by reference. The compositions containing the compounds can be administered for prophylactic and/or therapeutic treatments. In therapeutic applications, compositions are administered to a patient already suffering from a disease, as described above, in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. An amount adequate to accomplish this is defined as "therapeutically effective dose." Amounts effective for this use will depend on the severity of the disease and the weight and general state of the patient. In prophylactic applications, compositions containing the compounds of the invention are administered to a patient susceptible to or otherwise at risk of a particular disease. Such an amount is defined to be a "prophylactically effective dose." In this use, the precise amounts again depend on the patient's state of health and weight. As can be appreciated from the disclosure above, the present invention has a wide variety of applications. Accordingly, the following examples are offered by way of illustration, not by way of limitation. EXAMPLE 1 A. Solid Phase Peptide Synthesis Some peptides were synthesized using standard solid phase synthesis methods (see, e.g., Merrifield, J. Am. Chem. Soc. (1963) 85:2149) with the aid of an Applied Biosystems Inc. Model 431A peptide synthesizer. The synthesis was performed with PAL resin or HMP resin serving as an insoluble support that generated respectively a carboxamide or a carboxylic acid C-terminal in the final product. Most reagents, resins and protected amino acids (free or on resin) were purchased from Millipore or Applied Biosystems Inc. The fluorenylmethyloxycarbonyl group (Fmoc) was used for amino protection during the coupling procedure. Reactive side chain protections were as follows: Arg, 2,2,5,7,3- pentamethylchroman-6-sulfonyl (Pmc) ; Glu and Asp, O-t-butyl; Ser, Thr, Tyr, O-t-butyl; Trp. N-t-butyloxycarbonyl; His, Gin, N-trityl; and Cys, S-trityl. The peptides were assembled using the standard protocols of the Applied Biosystems Inc. System Software, version 1.0. Removal of the peptides from the resin and simultaneous deprotection of the side chain functions were achieved by treatment with reagent K or slight modifications thereof. The deprotected peptides were precipitated with diethylether. In all cases, purification was by preparative, reverse phase, HPLC on a C 18 bonded silicagel column. The homogenous peptides were characterized by Fast Atom Bombardment mass spectrometry or electrospray mass spectrometry and amino acid analysis, when applicable. Many analogued compounds were synthesized on a 0.25 mmoi scale using a Gilson AMS 422 multiple peptide synthesizer. The synthetic protocol was as follows: the solid support was a Knorr amide linker on methyl benzyhydryl amine resin (0.63 mmol/g); 4 equivalents of the Fmoc protected amino acids were used; Coupling was accomplished with PyBOP/HOBt and N-methyl morpholine; Fmoc deprotection at each step was accomplished with 20% piperidine, 30% toluene in DMF. The peptides were cleaved from the resin and all protecting groups removed by treating the peptide resin with 92% TFA, 5% H 2 0 and 3% ethanediol. Alternatively, many of the compounds were synthesized on an Applied Bioscience, Inc. model 430 peptide synthesizer. The synthetic protocol was as follows: the solid support was Rink amide linker on methylbenzyhydryl amine resin (0.55 mmol/g) ; 4 equivalents of Fmoc protected amino acids were used, and coupling was accomplished with HBTU/HOBt and DIEA. Fmoc deprotection at each step was achieved with 20% piperidine in NMP. The synthesis was stopped at Glu and divided into 0.1 mmoi aliquots and the N-terminus amino acid was coupled by the above protocol. The peptide was treated either with acetic anhydride or acetic acid HBTU/HOBt to give the N-acetyl derivative. ALternatively, the N-terminus was permethylated by treating the peptide resin with a large excess of methyl iodide in DMP with K 2 C0 3 . These compounds were all cleaved and deprotected as above. B. Synthesis of fMe 3 N)2Nap-EWTPaWY-(NMe)O-JY Boc-2-methylamino-4-cyano-L-butyric acid (Xue, et al. Tet. Letts. 36:55 (1995)) was oxidized to the δ- carboxamide via a modification of the procedure of Katritzky, et al.. Synthesis p.949 (1989). To a cooled solution of the nitrile (1.00 g, 4.13 mmoi) in MeOH (8ml) was added K 2 C0 3 (340 mg, 2.46 mmoi) and 30% H 2 0 2 (3 ml) dropwise. The reaction mixture was allowed to warm to room temperature with stirring. The reaction was monitored via TLC and additional H 2 0 2 was added as necessary. After 6 hours, the solvent was stripped to a puddle and saturated NaCl was added, cooled, the pH adjusted to 2.5-3 with 0.1 N HCl, and the product extracted into EtOAc. The organic layer was dried over MgS0 4 , filtered and evaporated to dryness. If necessary, the product can be purified by column chromatography or preparative HPLC to give a clear oil. The peptide was assembled on MeBHA resin via standard soid phase peptide synthesis conditions using Boc amino acids and DIC/HOBt for the couplings. The Boc-N-methyl- L-glutamine was coupled to Aze-Tyr(BrZ) -resin via the DIC/HOAt procedure of Angell, et al. Tet. Letts. 33:5981 (1994). The Boc-(NMe)Gin (2.5 eq.), DIC (2.5 eq.) and HOAt (2.5 eq.) were dissolved in DMF and added to the resin. The pH was monitored by holding moist pH paper over the reaction mixture, and it was kept above pH 9 with the addition of DIEA. After 2 hours, the resin was filtered, washed with DMF (3X) , 1:1 DCM/MeOH (3X) and DCM (3X) . After cleavage of the Boc group with TFA, Boc-tyr(Brz) was coupled to the secondary amine again with the DIC/HOAt procedure. The rest of the peptide was then assembled via standard solid phase peptide synthesis methods. The N-terminal Boc group was removed with TFA and permethylation of the N-terminal amine was performed by a modification of the procedure described in U.S. Patent No. 5,422,341. The terminal Boc group was removed by TFA/DCM and the resulting ammonium salt was neutralized as previously described. This peptide-resin was suspended in 20 ml DMF. To this suspension, CH 3 I (400 eq.) and K 2 C0 3 (20 eq.) were added. The reaction mixture was vortexed for 18 hours. The resin was filtered and washed with DMF (3X) , 1:1 water MeOH (3X) , water (2X) , DMF (3X) and MeOH (3X) . Deblocking and cleavage of the peptide from the resin was performed by standard HF procedures as described in Stewart and Young. The crude peptide was extracted from the resin with 50% aqueous HOAc, diluted with water and lyophilized. EXAMPLE 2 A. Prostaglandin E 2 (PGE 2 ) Response Assay Some of the peptides were tested for ability to block the IL-lα induced PGE 2 response in human foreskin fibroblasts. IL-lα is known to stimulate the production of PGE 2 by normal human fibroblasts, and an assay for PGE 2 is available from Amersham (see the instruction manual for the Prostaglandin E 2 [ 125 I] scintillation proximity assay (SPA) system, code RPA 539, incorporated herein by reference. Except as otherwise noted below, the assay was carried out according to the manufacturer's instructions and with the reagents supplied in the kit. For use in the assay, the cells should be actively growing at near confluence in 96 well tissue culture plates. Typically, cells were kept at about 60% confluency under "starved" conditions (low serum in the media) until needed for the assay. One day before the assay, as many wells as needed for the assay were seeded with about 1.5 x 10 4 cells per well in 100 μl of DMEM/F12 (a 1:1 mixture of the two medias, supplied by JRH Biosciences) plus 10% fetal bovine serum (FBS, supplied by Hyclone) and antibiotics (penicillin and streptomycin, P/S) to allow the cells to begin active growth. Each peptide in powder form was individually dissolved in DMEM/F12 containing 1% FBS and P/S to a final concentration of about 675 μM. 12 wells of a microtiter dish were typically used to assay each peptide. The media was removed from the cells (the cells were not washed) with a pipettor, and 140 μl of the peptide solution were added to half of the wells (i.e, peptide was added to a set of 6 wells and the other set of 6 wells served as the control) , and the plate was incubated for 30 minutes at 37°C. Then, 10 μl of a 15 pM solution of IL-lα (in the same DMEM solution as the peptide) were added to half of the wells containing peptide (i.e., typically 3 wells) and half of the wells with no peptide (i.e., 3 wells). About 10 μl of media were added to the wells which did not contain the IL-lα solution, and the plate was incubated for 6 hours at 37°C. Thus, for each peptide, the 3 wells of the microtiter dish contained no peptide and no IL-lα; 3 wells contained no peptide and IL-lα; 3 wells contained peptide and no IL-lα; and 3 wells contained peptide and IL-lα. About 100 μl of media from each microtiter well (the sample) were added to 100 μl of the methyl oximation reagent, and the resulting mixture was incubated at 60°C for one hour. About 300 μl of assay buffer were then added to each sample, and the sample was vortexed to ensure complete mixing. About 100 μl of the resulting sample were added to a labeled 1.5 ml Eppendorf™ tube. About 200 μl of assay buffer were added to two tubes labelled NSB (non-specific binding) . About 100 μl of assay buffer were added to two tubes labelled B 0 (B 0 is equal to the number of counts (cpm of 125 I) bound to the bead in the absence of PGE 2 ) . About 100 μl of tracer ( 125 I-PGE 2 -methyloximate; the methyloximate derivative of PGE 2 is more stable than PGE 2 ) are added to each tube, and 100 μl of anti-methyloximate PGE 2 antisera were added to all tubes except the NSB tubes. Then, about 100 μl of beads, which contain the scintillant and are coated with Protein A, were added to each tube. The Protein A binds to the antisera, and the antisera binds to the 125 I-PGE 2 -methyloximate. Unlabeled PGE 2 , the production of which is stimulated by IL-lα, competes with the 125 I-PGE 2 -methyloximate, thus reducing the total 125 I cpm bound to the bead. PGE 2 concentration was calculated from a standard curve as described in the Amersham PGE 2 SPA assay instruction manual. The results indicated that at least some of the peptides did inhibit the PGE 2 response to 1 pM IL-1 after 3 hours and 6 hours incubation. B. Epidermal Growth Factor Receptor Down Regulation Assay The protocol set forth in Bird and Saklatvala (1989) J. Immunol . 142:126-133, which is incorporated herein by reference, was also used to demonstrate the activity of the compounds of the present invention. This assay examines the effect of the compounds of the invention on the IL-1 induced down-regulation of the epidermal growth factor (EGF) receptor as measured by the binding of 125 I-labeled EGF to its receptor in normal human dermal fibroblasts (NHDF) . Incubation of the cells with the compounds of the present invention at 37°C, in the presence of IL-lα showed no decrease in the cells ability to subsequently bind subsaturating levels of 125 I-labeled epidermal growth factor, whereas incubation in the presence of IL-lα alone, resulted in a decrease in EGF binding. The table below lists the approximate concentration of representative peptides of the invention which blocked 50 % of the IL-1 induced down regulation of the EGF receptor. IC50 values are indicated symbolically by the symbols "-", "+", and "++". For example, those peptides which showed IC50 values in excess of 100 μM are indicated with a "- ". Those peptides which give IC50 values of less than or equal to 100 μM are given a "+", while those which give IC50 values of 500 nM or less are indicated with a "++". Those peptides which give IC50 values at or near the cutoff point for a particular symbol are indicated with a hybrid, e.g. "+/-". Those peptides for which IC50 values were not determined are listed as "N.D". Table 36 Peptide IC 50 ETPFTWEESNAYYWQPYALPL ++ TFVYWQJYALPL TFvYWQPYALPL 2 YIPFTWEESNAYYWQPYALPL ++ DGYDRWRQSGERYWQPYALPL ++ pY(INap) -pY-QJYALPL ++ TANVSSFEWTPGYWQPYALPL ++ FEWTPGYWQJYALPL ++ FEWTPGYWQPYALPLSD-NH 2 ++ FEWTPGYYQJYALPL ++ FEWTPGYWQJY-NH 2 + AcFEWTPGYWQJY-NH 2 + AcFEWTPGWYQJY-NH 2 *++/*+ AcFEWTPGYYQJY-NH 2 ++/*+ AcFEWTPaYWQJY-NH 2 + AcFEWTPaWYQJY-NH 2 + AcFEWTPaYYQJY-NH 2 + INap denotes 1-naphthylalanine and NH 2 denotes an amide group, e.g., a carboxamide. C. Peptide Effects on IL-1 Induced E-Selectin (HUVEC Cells) The compounds of the present invention were assayed for their ability to inhibit the expression of IL-1 induced E- selectin in HUVEC cells (human umbilical vein endothelial cells) . HUVEC cells are grown to confluency in the wells of a 24-well microtiter plate. The compounds were serially diluted in DMEM/F12 + 0.1 % BSA ("SFM") with 120 pM IL-lα. The cells were washed and then incubated with IL-lα and the compound to be tested for 15 minutes. The cells were again washed and incubated in SFM for 4 hours. The cells were washed and incubated with anti-selectin antibody for 30 minutes. Following antibody incubation, the cells were incubated with 125 j p ro tein A and washed. The amount of 125 I bound to the cells was then determined. The concentration of compounds required to inhibit 50% of IL-1 induced E-selectin expression is shown below. d-Valine is used at the 3-position. Table 37 Peptide IC 50 FEWTPGYYQJYALPL ++ FEWTPGYWQJYALPL ++ FEWTPGWYQJYALPL ++ TANVSSFEWTPGYWQPYALPL ++ AcFEWTPGYWQJY-NH 2 ++ AcFEWTPGWYQJY-NH 2 ++ AcFEWTPGYYQJY-NH 2 ++ AcFEWTPaYWQJY-NH 2 ++ AcFEWTPaWYQJY-NH 2 ++ AcFEWTPaYYQJY-NH 2 ++ D. Other Assays Other biological assays that can be used to demonstrate the activity of the compounds of the present invention are disclosed in Dripps et al . , (1991) J . Biol . Chem . 266(16) :10331-10336, and Bird et al . (1991) J. Biol . Chem . 266 (33) :22662-22670, each of which is incorporated herein by reference. EXAMPLE 3 Determination of Concentration Effecting Inhibition of IL-lα Binding This example provides the results of experiments conducted to determine an approximate IC 50 for certain peptides of the invention. IC 50 as used herein refers to the concentration of a compound which will inhibit 50 % of the binding between a receptor and its ligand, e.g. IL-lRtI and IL-1. Stock solutions of each peptide were prepared. The appropriate amount of the peptide was dissolved in DMSO, and then nineteen volumes of binding buffer (RPMI 1640, 1% BSA, 20 mM HEPES, pH 7.2-7.3, and 0.1% sodium azide) were added to yield a 1 mM peptide, 5% DMSO stock solution. One assay utilized a truncated IL-lRtI which had been immobilized on 96-well plates with an appropriate antibody, typically a non-blocking high affinity antibody. In other assays, cells expressing "full-length" IL-lRtI were used with results that yielded IC 50 values about 5 to 10 fold lower than those determined using the truncated receptor. The cells were seeded onto Falcon 3072 96-well plates at about 10 5 cells per well, and the plates were incubated overnight at 37°C in media containing serum. The following morning, the cells were checked to ensure that the cells were confluent and adhered to the bottom of the wells. According to either assay protocol, the plates were then washed three times with binding buffer, and then 50 μl of binding buffer and 25 μl of a peptide solution (either the stock solution or a dilution thereof; each stock was subjected to five three fold dilutions) were added to each well. Then 25 μl of binding buffer containing 125 I-IL-lα (final concentration of 90 pM) were added to each well to begin the assay. Each assay was carried out in duplicate. The plates were then incubated for two hours at 4°C. For peptides having particularly high affinities, the assay was run in 24 well plates allowing for higher levels of ligand (possible total volume of 2.5 ml instead of 100 μl in the 96 well plate), thereby minimizing the potential for ligand depletion. After the two hour incubation, the wells were rinsed three times with ice cold PBS (a semi-automated cell harvesting device was used to conduct the rinse) . The receptors or cells were then detached from the plates by adding 100 μl of 0.1 N NaOH to each well and incubating the plates at room temperature for 20 minutes. After the 20 minute incubation, about 75 μl of the suspension was counted on a gamma counter, and the IC 50 for each peptide was determined using computer assistance and the results of the gamma counting. All publications and patent documents cited in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication or patent document were so individually denoted.

Claims: WE CLAIM : 1. A compound that binds to an interleukin-1 type I receptor, said compound comprising: a molecular weight less than about 3000 Daltons; a binding affinity to an interleukin-1 type I receptor as expressed by an IC 50 standard of no more than about 2.5 mM; wherein the binding of said compound to said interleukin-1 type I receptor is competitively inhibited by a compound of 11 to 40 amino acids in length that binds to the interleukin-1 type I receptor and that comprises a core sequence of amino acids: Z 31 X 41 Z 32 Z 33 Z 34 Z 35 Z 36 Z 42 Z 37 Z 38 where each letter represents an amino acid or an analog thereof; X is any natural or unnatural amino acid; Z 31 is selected from phenylalanine, tyrosine, 1- naphthylalanine, 2-naphthylalanine, p-benzoyl-L-phenylalanine, tryptophan, histidine, homophenylalanine, 3-pyridylalanine, thienylalanine, benzothienylalanine, cyclohexylalanine, phenylglycine, D-phenylalanine, tetrahydroisoquinoline, tetrahydro- -carboline, D-des-aminophenylalanine, L-des- aminophenylalanine, and substituted amines thereof; Z 32 is selected from alanine, threonine, valine, allothreonine, isoleucine, serine and norleucine; Z 33 is selected from proline, azetidine, sarcosine, alanine, D-proline, glycine, N-methylalanine and pipecolic acid; Z 34 is selected from glycine, asparagine, any D- amino acid, sarcosine and aminoisobutyric acid; Z 35 is a natural or unnatural amino acid; Z 36 is selected from tyrosine, tryptophan, phenylalanine, phosphotyrosine, p-benzoyl-L-phenylalanine, 1- naphthylalanine, 4-nitrophenylalanine, 4-aminophenylalanine, 4-methoxyphenylalanine and tetrahydro-β-carboline; Z 37 is a cyclic amino acid; Z 38 is selected from tyrosine, substituted tyrosine, tyrosinamide, substituted tyrosinamide, l-naphthylalanine, p- benzoyl-L-phenylalanine, phenylalanine, 4-aminophenylalanine, 4-methoxyphenylalanine, 4-nitrophenylalanine and 3- pyridylalanine; Z 41 is selected from tryptophan, phenylalanine, 4- aminophenylalanine, 4-methoxyphenylalanine, 4- nitrophenylalanine and 3-pyridylalanine; and Z 42 is selected from glutamine and N- methylglutamine. 2. The compound of claim 1, wherein said compound comprises an affinity to an interleukin-1 type I receptor as expressed by an IC 50 standard of no more than about 100 μM. 3. The compound of claim 1, wherein said compound comprises an affinity to an interleukin-1 type I receptor as expressed by an IC 50 standard of no more than about 1 μM. 4. The compound of claim 1, wherein said compound blocks binding of interleukin-1 to an interleukin-1 type I receptor. 5. The compound of claim 1, wherein said compound is a peptide. 6. A compound of 11 to 40 amino acids in length that binds to the interleukin-1 type I receptor, said compound comprising the general sequence: Z 31 XZ 41 Z 32 Z 33 Z 34 Z 35 Z 36 Z 42 Z 37 Z 38 where each letter represents an amino acid or an analog thereof; X is any natural or unnatural amino acid; Z 31 is selected from phenylalanine, tyrosine, 1- naphthylalanine, 2-naphthylalanine, p-benzoyl-L-phenylalanine, tryptophan, histidine, homophenylalanine, 3-pyridylalanine, thienylalanine, benzothienylalanine, cyclohexylalanine, phenylglycine, D-phenylalanine, tetrahydroisoquinoline, tetrahydro- / 3-carboline, D-des-aminophenylalanine, L-des- aminophenylalanine, and substituted amines thereof; Z 32 is selected from alanine, threonine, valine, allothreonine, isoleucine, serine and norleucine; Z 33 is selected from proline, azetidine, sarcosine, alanine, D-proline, glycine, N-methylalanine and pipecolic acid; Z 34 is selected from glycine, asparagine, any D- amino acid, sarcosine and aminoisobutyric acid; Z 35 is a natural or unnatural amino acid; Z 36 is selected from tyrosine, tryptophan, phenylalanine, phosphotyrosine, p-benzoyl-L-phenylalanine, 1- naphthylalanine, 4-nitrophenylalanine, 4-aminophenylalanine, 4-methoxyphenylalanine and tetrahydro-β-carboline; Z 37 is a cyclic amino acid; Z 38 is selected from tyrosine, substituted tyrosine, tyrosinamide, substituted tyrosinamide, l-naphthylalanine, p- benzoyl-L-phenylalanine, phenylalanine, 4-aminophenylalanine, 4-methoxyphenylalanine, 4-nitrophenylalanine and 3- pyridylalanine; Z 1 is selected from tryptophan, phenylalanine, 4- aminophenylalanine, 4-methoxyphenylalanine, 4- nitrophenylalanine and 3-pyridylalanine; and Z 2 is selected from glutamine and N- methylglutamine. 7. The compound of claim 6, wherein Z 37 is selected from the group consisting of proline and azetidine. 8. The compound of claim 6, wherein said compound is selected from the group consisting of: FEWTPGYWQPY-NH 2 ; FEWTPGYWQJY-NH 2 ; FEWTPGWYQJY-NH 2 ; ACFEWTPGWYQJY-NH 2 ; FEWTPGW-pY-QJY-NH 2 ; FAWTPGYWQJY-NH 2 ; FEWAPGYWQJY-NH 2 ; FEWVPGYWQJY-NH 2 ; FEWTPGYWQJY-NH 2 ; AcFEWTPGYWQJY-NH 2 ; FEWTPaWYQJY-NH 2 ; FEWTP-Sar-WYQJY-NH 2 ; FEWTPGYYQPY-NH 2 ; FEWTPGWWQPY-NH 2 ; FEWTPNYWQPY-NH 2 ; FEWTPvYWQJY-NH 2 ; FEWT-Pec-GYWQJY-NH 2 ; FEWTP-Aib-YWQJY-NH 2 ; FEWT-Sar-GYWQJY-NH 2 ; FEWTPGYWQPYALPL; FEWTPGYYQJ-Bpa-NH 2 ; AcFEWTPGYYQJ-Bpa-NH 2 ; FEWTPGY-Bpa-QJY-NH 2 ; AcFEWTPGY-Bpa-QJY- NH 2 ; FEWTPG-Bpa-YQJY-NH 2 ; AcFEWTPG-Bpa-YQJY-NH 2 ; FE-Bpa- TPGYYQJY-NH 2 ; AcFE-Bpa-TPGYYQJY-NH 2 ; Bpa-EWTPGYYQJY-NH 2 ; AcBpa-EWTPGYYQJY-NH 2 ; lNap-EWTPGYYQJY-NH 2 ; YEWTPGYYQJY-NH 2 ; FEWVPGYYQJY-NH 2 ; FEWTPsYYQJY-NH 2 ; FEWTPnYYQJY-NH 2 ; (Me 3 N)lNap-EWTPaWYQJY; AcFEWTPaWYQJY; FEWTPnYYQJY; AcFEWTPGYYQJY, (Me 3 N) F-EWTPGWYQJY, AcFEWTPaYYQJY; Ac2Nap- EWTPaYWQJY; (Me 3 N) 2Nap-EWTPaWYQJY; FEWTPGWYQJY; AcWEWTPaYWQJY; AcY(OCH 3 ) -EWTPaYWQJY; AcF(4-N0 2 ) -EWTPaYWQJY; (Me 2 N)F-EWTPaWYQJY; (Me 2 N) F-EWTPaWYQJY; AcYEWTPaYWQJY; (Me 3 N)Bta-EWTPaWYQJY; AcFEWTPaWYQJY; (Me 3 N) F-EWTPaQJY; AcFEWTPaFWQJY; HO-(R) -F-EWTPGWYQJY; (Me 3 N) 2Nap-EWTPaWY-(NMe)Q-JY; FEW-Nle-PGYWQJY; AcFEWTPdWYQJY; AcFEWTPaY-(4NH 2 ) F-QJY; FEW-alloThr-PGYWQJY; AcFEWTPa-(4-N0 2 ) F-WQJY; AcFEWTPkWYQJY; AcFEWTPa-(4-NH 2 ) F-YQJY; Ac-FQWTPaYWQJY; (Me 3 N)Tha-EWTPaWYQJY; AcPya-EWTPaYWQJY; AcFEWTPa-(4-NH 2 ) F-WQJY; NH 2 (=0) F-EWTPaYWQJY; Ac-Thc-EWTPaYWQJY; AcFEWTPa-Y(OCH 3 ) -WYQJY; HO-(S) -F-EWTPGWYQJY; AcF-E(OCH 3 ) -WTPaYWQJY; AcFEWTPaYWQJF; AcFEWTPaY-(4-N0 2 ) F-QJY; AcFEWTPaW-Y(OCH 3 ) -QJY; ACFEWTP-(NMe-a) -WYQJY; AcFEWTPaYWQJ-(4-NH 2 ) F; FEWTJGYWQJY; AcFMWTPaYWQJY; AcFDWTPaYWQJY; AcFEWTPa-Y(OCH 3 ) -YQJY; AcFEWT- (NMe-A) -aWYQJY; AcFEWTPfWYQJY; AcFEWTPaY-Pya-QJY; AcFHWTPaYWQJY; AcFEWIPaYWQJY; AcfEWTPaYWQJY; FEWSPGYWQJY; FEWTAGYWQJY; FEWTpGYWQJY; ACHEWTPaYWQJY; Ac-hmoF-EWTPaYWQJY; AcFEWAPpYWQJY; AcFEW-Nle-PaYWQJY; AcFEYTpaYWQJY; AcFEWTPa-Thc- YQJY; AcFE-(4-N0 2 )F-TPaYWQJY; des(NH 2 ) F-EWTPaWYQJY; FE-lNap- TPGWYQJY; AcFEFTPaYWQJY; AcFEWTPaYWQJY-Y(OCH 3 ) ; AcFEWTPaY-Thc- QJY; AcFEWTPaWYQJ-Pya; Ac-Tiq-EWTPaWYQJY; Ac-Cha-EWTPaWYQJY; and AcFE-Pya-TPaYWQJY; where AcF is acetylated phenylalanine, Y-NH 2 is tyrosinamide, -pY- is phosphotyrosine, -Sar- is sarcosine, - Pec- is pipecolic acid, -Aib- is aminoisobutyric acid, INap is l-naphthylalanine, 2Nap is 2-naphthylalanine, Pya is pyridylalanine; Cha is cyclohexylalanine, NMe-A is N- methylalanine, Tha is thienylalanine, Bta is benzothienylalanine, The is tetrahydro-/3-carboline, allothr is allothreonine, having the opposite stereochemistry from threonine at the C3 position, Tiq is tetrahydroisoquinoline, hmoF is homophenylalanine, (4-NH 2 )F is 4-aminophenylalanine, (4-N0 2 )F is 4-nitrophenylalanine, (4-CH 3 0)F is 4- methoxyphenylalanine, Bpa is p-benzoyl-L-phenylalanine and AcBpa is acetylated p-benzoyl-L-phenylalanine. 9. A compound of 14 to 40 amino acids in length that binds to the interleukin-1 type I receptor and comprises the sequence FTWEESNAYYWQJY-NH 2 ; where each letter represents the standard one letter abbreviation for an amino acid. 10. A compound of 10 to 40 amino acids in length that binds to the interleukin-1 type I receptor and comprises the sequence pY(INap)pYQJYALPL, where INap is l-naphthylalanine and pY is phosphotyrosine. 11. A compound that binds to an interleukin-1 type I receptor, said compound comprising a molecular weight less than about 3000 Daltons; a binding affinity to an interleukin-1 type I receptor as expressed by an IC 50 standard of no more than about 2.5 mM; and wherein the binding of said compound to said interleukin-1 type I receptor is competitively inhibited by a compound of 11 to 40 amino acids in length that binds to the interleukin-1 type I receptor and comprises a core sequence of amino acicis z 2 NZ 2 9 z 2 rZ 2£ Z 2 z 2 o 2g Z Q n where Z 23 is D or Y; Z 24 is D, S or T; Z 39 is S, T or A; Z 25 is S or W; Z 26 is S or Y; Z 27 is D, Q, E or V; Z 28 is N, S, K, H or W; Z 29 is F or L; Z 30 is D, N, S or L; and Z 40 is L, I, Q, M or A. 12. The compound of claim 11, wherein said compound comprises an affinity to an interleukin-1 type I receptor as expressed by an IC 50 standard of no more than about 100 μM. 13. The compound of claim 11, wherein said compound comprises an affinity to an interleukin-1 type I receptor as expressed by an IC 50 standard of no more than about 1 μM. 14. The compound of claim 11, wherein said compound blocks binding of interleukin-1 to an interleukin-1 type I receptor. 15. The compound of claim 11, wherein said compound is a peptide. 16. A compound of 11 to 40 amino acids in length that binds to the interleukin-1 type I receptor and comprises the sequence Z 23^ Z 24 Z 39 Z 25 Z 26 Z 27 Z 28 Z 29 30 Z 40 where Z 23 is D or Y ; Z 24 is D , S or T ; Z 3g is S , T or A ; Z 25 is S or W; Z 26 is S or Y ; Z 27 is D , Q , E or V; Z 28 is N , S , K , H or W ; Z 29 is F or L ; Z 30 is D , N , S or L; and Z 40 is L , I , Q , M or A. 17. The compound of claim 11, wherein said compound is selected from the group consisting of DNSSWYDSFLL; DNTAWYESFLA; DNTAWYENFLL; PAREDNTAWYDSFLIWC; TSEYDNTTWYEKFLASQ SQIPDNTAWYQSFLLHG SPFIDNTAWYENFLLTY; EQIYDNTAWYDHFLLSY TPFIDNTAWYENFLLTY TYTYDNTAWYERFLMSY; TMTQDNTAWYENFLLSY TIDNTAWYANLVQTYPQ TIDNTAWYERFLAQYPD; HIDNTAWYENFLLTYTP SQDNTAWYENFLLSYKA QIDNTAWYERFLLQYNA; NQDNTAWYESFLLQYNT TIDNTAWYENFLLNHNL and HYDNTAWYERFLQQGWH. 18. The compound of claim 1, 6, 9, 10, 11 or 16 that is conjugated to a cytotoxic agent. 19. A pharmaceutical composition comprising the compound of claim 1, 6, 9, 10, 11 or 16, in combination with a pharmaceutically acceptable carrier. 20. A method for treating a patient having a disorder that is susceptible to treatment with an IL-1 inhibitor. comprising administering to said patient, a therapeutically effective dose or amount of the compound of claim 1, 6, 9, 10, 11 or 16. 21. A method of antagonizing action of Interleukin-1 on an interleukin-1 type I receptor, said method comprising contacting said receptor with the compound of claim 1, 6, 9, 10, 11 or 16. 22. A method of photolabeling an IL-1 type I receptor, the method comprising: contacting the receptor with a compound of claim 6, wherein at least 1 of Z 31 , Z 35 , Z 36 or Z 38 are p-benzoyl-L- phenylalanine; and photolyzing the compound whereby the compound is covalently bound to the receptor.

Inventors: BALDWIN DAVID, BARRETT RONALD W, BOVY PHILIPPE R, DHARANIPRAGADA RAMALINGA, JACOBS JEFF W, LEAHY ELLEN M, POTTORF RICHARD S, TOMLINSON RONALD C, YANOFSKY STEPHEN D, BALDWIN, DAVID, BARRETT, RONALD, W., BOVY, PHILIPPE, R., DHARANIPRAGADA, RAMALINGA, JACOBS, JEFF, W., LEAHY, ELLEN, M., POTTORF, RICHARD, S., TOMLINSON, RONALD, C., YANOFSKY, STEPHEN, D.
Applicants: AFFYMAX TECH NV, BALDWIN DAVID, BARRETT RONALD W, BOVY PHILIPPE R, DHARANIPRAGADA RAMALINGA, JACOBS JEFF W, LEAHY ELLEN M, POTTORF RICHARD S, TOMLINSON RONALD C, YANOFSKY STEPHEN D, AFFYMAX TECHNOLOGIES N.V., BALDWIN, DAVID, BARRETT, RONALD, W., BOVY, PHILIPPE, R., DHARANIPRAGADA, RAMALINGA, JACOBS, JEFF, W., LEAHY, ELLEN, M., POTTORF, RICHARD, S., TOMLINSON, RONALD, C., YANOFSKY, STEPHEN, D.
Application year: 1996
Main classification: A61K38
IPC codes: A61K38, C07K14