Compounds for inhibition of MMP13-substrate interactions and methods of use thereof to treat osteoarthritis and cartilage degeneration

摘要

The present invention provides compounds for disrupting the binding of a matrix metalloprotease (MMP) protein to a substrate protein at an interaction site other than the protease catalytic site. In particular the inventive compounds inhibit the MMP's ability to cleave a substrate protein. In some cases the compound may prevent activation of transforming growth factor beta (TGFβ). The compounds are preferably polypeptide fragments of the hemopexin-like domain of the MMP, but may be mimetics thereof or peptides or mimetics of the portion of the MMP substrate protein to which the MMP interacts.

主权项

1. A synthetic compound with binding affinity for a matrix metalloprotease (MMP) substrate protein, wherein the compound is able to competitively inhibit binding of MMP13 to the substrate protein, and
wherein the compound comprises a peptide or peptide mimetic of at least 80% identity to amino acids 17-42 of SEQ ID NO:44, and wherein sequences 17-26 and 37-42 each include 1 or zero changes.