Inhibitors of beta integrin-G protein alpha subunit binding interactions
View Patent ↗Provided herein are compounds that inhibit a binding interaction between a β integrin and a G protein subunit, as well as compositions, e.g., pharmaceutical compositions, comprising the same, and related kits. In some embodiments, the compound is an antibody or antibody analog, and, in other embodiments, the compound is a peptide or peptide analog. Also provided are methods of using the compounds, including methods of treating or preventing a medical condition, such as stroke, heart attack, cancer, or inflammation.
1. A peptide comprising FEEERA (SEQ ID NO: 87)
wherein the peptide is a 6-mer, 7-mer, 8-mer, or 9-mer.
2. A peptide consisting essentially of or consisting of FEEERA (SEQ ID NO: 87).
3. The peptide of claim 1 , comprising a fatty acid.
4. The peptide of claim 3 , wherein the fatty acid is a C4 to C30 fatty acid.
5. The peptide of claim 4 , wherein the fatty acid is covalently attached to the N-terminus of the peptide.
6. The peptide of claim 5 , wherein the N-terminus of the peptide is the Phe of SEQ ID NO:87 and is covalently attached to a fatty acid.
7. A micelle comprising a peptide of claim 3 and at least one lipid.
8. The micelle of claim 7 , comprising a lipid covalently attached to a water soluble polymer and a lipid free of a water soluble polymer.
9. The micelle of claim 8 , wherein the lipid covalently attached to a water soluble polymer is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000], the lipid free of a water soluble polymer is phophatidylcholine.
10. The micelle of claim 9 , wherein the N-terminus of the peptide is the Phe of SEQ ID NO:87 and is covalently attached to a C14 fatty acid or a C16 fatty acid.
11. A composition comprising the micelle of claim 7 and an aqueous solution.
12. A pharmaceutical composition comprising the peptide of claim 1 , or a micelle comprising the peptide of claim 1 , and a pharmaceutically acceptable carrier, diluent, or excipient.
13. The pharmaceutical composition of claim 12 , wherein the N-terminus of the peptide is the Phe of SEQ ID NO:87 and is covalently attached to a C14 fatty acid or a C16 fatty acid.
14. A conjugate comprising a peptide and a fatty acid, wherein the peptide consists of FEEERA (SEQ ID NO: 87).
15. The conjugate of claim 14 , wherein the fatty acid is a C4 to C30 fatty acid.
16. The conjugate of claim 15 , wherein the fatty acid is covalently attached to the N-terminus of the peptide.
17. A micelle comprising a conjugate of claim 14 and at least one lipid.
18. A composition comprising the micelle of claim 17 and an aqueous solution.
19. A pharmaceutical composition comprising the conjugate of claim 14 , or a micelle comprising the conjugate of claim 14 , and a pharmaceutically acceptable carrier, diluent, or excipient.
20. The pharmaceutical composition of claim 19 , wherein the Phe at position 1 of the peptide is covalently attached to a C14 fatty acid or a C16 fatty acid.
21. The peptide of claim 1 , wherein the fatty acid is a C12 to C20 fatty acid.
22. The peptide of claim 21 , wherein the fatty acid is a C14 fatty acid, C16 fatty acid, or C18 fatty acid.
23. The peptide of claim 22 , wherein the fatty acid is a C14 fatty acid.
24. The conjugate of claim 15 , wherein the fatty acid is a C12 to C20 fatty acid.
25. The conjugate of claim 21 , wherein the fatty acid is a C14 fatty acid, C16 fatty acid, or C18 fatty acid.
26. The conjugate of claim 25 , wherein the fatty acid is a C14 fatty acid.