Claims
- 1. A peptide that binds to a member of the mammalian selectin family and inhibits the binding of a carbohydrate to said selectin.
- 2. The peptide of claim 1, wherein said member of the mammalian selectin family is a cell-surface, carbohydrate-binding protein.
- 3. The peptide of claim 2, wherein said selectin is selected from E-selectin, P-selectin, or L-selectin.
- 4. The peptide of claim 3, wherein said selectin is E-selectin.
- 5. The peptide of claim 1, wherein said peptide has a conformation selected from linear, cyclic or multivalent.
- 6. The peptide of claim 3, wherein said peptide inhibits the binding of either one or both of sLex or sLea to said selectin.
- 7. A peptide comprising a heptapeptide selected from the group consisting of:
-IX1LX2QX3R- (SEQ ID NO:1); -X1X2LLX3AR- (SEQ ID NO:2); and -IX1LLX2X3R- (SEQ ID NO:33).
- 8. The peptide of claim 7, wherein said peptide comprises a heptapeptide selected from the group consisting of:
-IX1LX2QAR- (SEQ ID NO:3); -IX1LLQX2R- (SEQ ID NO:4); and -IX1LLX2AR- (SEQ ID NO:5).
- 9. The peptide of claim 8, wherein said peptide comprises an amino acid sequence -IXLLQAR- (SEQ ID NO:6).
- 10. The peptide of claim 9, wherein said peptide comprises an amino acid sequence selected from the group consisting of -IELLQAR- (SEQ ID NO:7), and -ISLLQAR- (SEQ ID NO:8).
- 11. The peptide of claim 8, wherein said peptide comprises an amino acid sequence selected from the group consisting of -IDLMQAR- (SEQ ID NO:9), -IILLQGR- (SEQ ID NO:10), and -ISLLGAR- (SEQ ID NO:11).
- 12. The peptide of claim 7, wherein said peptide comprises an amino acid sequence selected from the group consisting of -FSLLDAR- (SEQ ID NO:12), and -IFLLWQR- (SEQ ID NO:34).
- 13. A composition comprising the peptide of claim 1 or claim 7.
- 14. The composition of claim 13, wherein said composition is a pharmaceutical composition.
- 15. A method of inhibiting a carbohydrate or an antibody from binding to a selectin comprising contacting the selectin with the composition of claim 13.
- 16. The method of claim 15, wherein said carbohydrate is on the surface of a cell.
- 17. The method of claim 16, wherein said cell is a tumor cell or a leukocyte.
- 18. The method of claim 15, wherein said selectin is on the surface of a cell.
- 19. The method of claim 18, wherein said cell is a vascular endothelial cell.
- 20. The method of claim 15, wherein said contacting results in the inhibition of tumor cell metastasis or inhibition of inflammation in a subject.
- 21. A method of inhibiting a first cell from binding to an endothelial cell comprising contacting the endothelial cell with the composition of claim 13.
- 22. The method of claim 21, wherein said peptide binds to a selectin on the surface of said endothelial cell.
- 23. The method of claim 21, wherein said peptide inhibits a carbohydrate on the surface of the cell from binding to said selectin.
- 24. The method of claim 23, wherein said selectin is E-selectin.
- 25. The method of claim 23, wherein said carbohydrate is either one or both of sLea or sLex.
- 26. The method of claim 25, wherein said first cell is a leukocyte or a tumor cell.
- 27. A method of inhibiting tumor cell metastasis in a subject, comprising administering an effective amount of the pharmaceutical composition of claim 14.
- 28. A method of inhibiting inflammation in a subject, comprising administering an effective amount of the pharmaceutical composition of claim 14.
- 29. A conjugate comprising the peptide of claim 1 or of claim 7 linked to a moiety.
- 30. The conjugate of claim 29, wherein said moiety is a cytotoxic agent or a detectable moiety.
- 31. The conjugate of claim 39, wherein said cytotoxic agent is a cancer chemotherapeutic agent.
- 32. The conjugate of claim 29, wherein said moiety is selected from the group consisting of a chambered microdevice, a liposome, a cell, a grafted polypeptide and a virus.
- 33. The peptide of claim 1, wherein said peptide is a hexapeptide selected from the group consisting of:
-X1LLX2X3R- (SEQ ID NO:36), -X1LX2QX3R- (SEQ ID NO:14), -X1LX2QAR- (SEQ ID NO:15), -X1LLX2AR- (SEQ ID NO:16), and -X1LLQX2R- (SEQ ID NO:17).
- 34. The peptide of claim 1, wherein said peptide is a pentapeptide selected from the group consisting of:
-LLX1X2R- (SEQ ID NO:35), -LX1QX2R- (SEQ ID NO:24), -LXQAR- (SEQ ID NO:25), -LLXAR- (SEQ ID NO:26), and -LLQXR- (SEQ ID NO:27).
Government Interests
[0001] This invention was funded in part by NIH Grant No. CA71932 and CA33000. Accordingly, the United States government has certain rights in the invention.
Divisions (1)
|
Number |
Date |
Country |
Parent |
09232484 |
Jan 1999 |
US |
Child |
10193979 |
Jul 2002 |
US |