T cell antigen receptor peptides
View Patent ↗The present invention provides peptides which affect T-cells, presumably by action on the T-cell antigen receptor. The present invention further relates to the therapy of various inflammatory and autoimmune disease states involving the use of these peptides. Specifically, the peptides are useful in the treatment of disorders where T-cells are involved or recruited. In one aspect the peptides have the formula: R1-A—B—A—R2 in which A is a hydrophobic amino acid or a hydrophobic peptide sequence comprising between 2 and 10 amino acids; B is a charged amino acid; R1 is NH2 and R2 is COOH. In another aspect the peptides have the formula: R1-A—B—C—R2 in which A is a peptide sequence of between 0 and 5 amino acids; B is cysteine; C is a peptide sequence of between 2 to 10 amino acids; R1 is NH2; and R2 is COOH.
1. A peptide that inhibits T-cell antigen receptor (TCR function, which has a formula selected from the group consisting of formula
NH2-Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-Phe-OH (SEQ ID NO. 6),
NH2-Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-OH (SEQ ID NO. 7),
NH2-Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH (SEQ ID NO. 8),
NH2-Leu-Gly-Ile-Leu-Leu-Leu-Lys-Val-OH (SEQ ID NO. 9),
NH2-Ile-Leu-Leu-Gly-Lys-Ala-Thr-Leu-Tyr-OH (SEQ ID NO. 10),
NH2-Met-Gly-Leu-Arg-Ile-Leu-Leu-Leu-OH (SEQ ID NO. 11),
NH2-Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-COOH (SEQ ID NO. 12)
NH2-Ile-Ile-Val-Thr-Asp-Val-Ile-Ala-Thr-Leu-OH (SEQ ID NO. 13)
NH2-Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH (SEQ ID NO. 14),
NH2-Phe-Leu-Phe-Ala-Glu-Ile-Val-Ser-Ile-OH (SEQ ID NO. 15)
NH2-Ala-Gly-Phe-Asn-Leu-Leu-Met-Thr-COOH (SEQ ID NO. 16).
2. A peptide which inhibits TCR function, wherein the peptide has the formula
NH2-Ile-Ile-Val-Thr-Asp-Val-Ile-Ala-Thr-Leu-OH (SEQ ID NO. 13),
NH2-Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH (SEQ ID NO. 14), or
NH2-Phe-Leu-Phe-Ala-Glu-Ile-Val-Ser-Ile-OH (SEQ ID NO. 15).
3. A peptide which inhibits TCR function, wherein the peptide is derived from the TCR-α intracellular chain and comprises the formula:
NH2-Ala-Gly-Phe-Asn-Leu-Leu-Met-Thr-COOH (SEQ ID NO. 16).
4. A peptide which inhibits T-Cell antigen receptor function wherein the peptide has the formula:
NH2-Tyr-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH (SEQ ID NO. 17), or
NH2-Trp-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH (SEQ ID NO. 18), or
NH2-Tyr-Gly-Arg-Ala-Asp-Cys-Ile-Thr-Ser-OH (SEQ ID NO. 19), or
NH2-Ser-Ser-Asp-Val-Pro-Cys-Asp-Ala-Thr-Leu-Thr-OH (SEQ ID NO. 20).
5. The peptide according to claim 1 which has the formula:
NH2-Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-Phe-OH (SEQ ID NO. 6),
NH2-Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-OH (SEQ ID NO. 7),
NH2-Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH (SEQ ID NO. 8),
NH2-Leu-Gly-Ile-Leu-Leu-Leu-Lys-Val-OH (SEQ ID NO. 9),
NH2-Ile-Leu-Leu-Gly-Lys-Ala-Thr-Leu-Tyr-OH (SEQ ID NO. 10),
NH2-Met-Gly-Leu-Arg-Ile-Leu-Leu-Leu-OH (SEQ ID NO. 11), or
NH2-Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-COOH (SEQ ID NO. 12).
6. A therapeutic composition comprising a peptide as claimed in claim 1 , and a pharmaceutically acceptable carrier.
7. A method of treating a subject suffering from a condition selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, psoriasis, inflammatory conditions, myositis, and ankylosing spondylitis, the method comprising the step of administering an effective amount of a composition as claimed in claim 6 to the subject.
8. A method according to claim 7 , in which the condition is rheumatoid arthritis or psoriasis.