Peptide analogs of alpha-melanocyte stimulating hormone

摘要

Provided herein are stable peptide analogs of the native alpha-melanocyte stimulating hormone (α-MSH) having selectivity for the melanocortin 1 receptor (MC1R). Also provided herein are pharmaceutical preparations of the α-MSH peptide analogs, as well as methods of using these analogs in the treatment of medical and veterinary conditions involving MC1R.

主权项

1. A method of treating an autoimmune disease or condition in a subject in need thereof, comprising administering to said subject a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a substantially pure compound that selectively binds melanocortin 1 receptor (MC1R), said compound comprising a polypeptide (SEQ ID NO:9) having the sequence:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13, wherein Xaa1 is D-Val, D-Ala or D-Lys;
Xaa2 is D-Pro, D-Ala or D-Lys;Xaa3 is D-Lys, D-Orn, D-Nle, D-Ala or D-Lys;Xaa4 is Gly, or D-Ala;Xaa5 is D-Trp, Trp, D-3-benzothienyl-Ala, D-5-hydroxy-Trp, D-5-methoxy-Trp, D-Phe,-or-D-Ala;Xaa6 is D-Arg, D-His, or D-Ala;Xaa7 is D-Cha, D-Phe, Phe, D-4-fluoro-Phg, D-3-pyridyl-Ala, D-Thi, D-Trp, D-4-nitro-Phe, or D-Ala;Xaa8 is D-His, His, D-Arg, Phe, or D-Ala;Xaa9 is D-Glu, D-Asp, D-citrulline, D-Ser, or D-Ala;Xaa10 is D-Met, D-buthionine, D-Ile, or D-Ala;Xaa11 is D-Ser, D-Ile or D-Ala;Xaa12 is D-Tyr, D-Ser, or D-Ala; andXaa13 is D-Ser or D-Ala; wherein no more than one Xaa1-13 is D-Ala except when Xaa1-3 are all D-Ala, and no more than one Xaa1-13 is an L-amino acid; or a pharmaceutically acceptable salt thereof, wherein said autoimmune disease or condition is selected from the group consisting of multiple sclerosis, diabetes type I, aplastic anemia, Grave's disease, celiac disese, Crohn's disease, lupus, arthritis, osteoarthritis, autoimmune uveitis and myasthenia gravis.