Phosphinic Peptide Matrix Metalloproteinase-9 Inhibitors by Solid-Phase Synthesis Using a Building Block Approach

Abstract

Substrates of matrix metalloproteinase-9 (MMP-9) having Gly and Leu in the P1and P1′ position can be converted into highly potent inhibitors by incorporation of a phosphinic -GΨ{P(O)OHCH2}L- moiety (see figure). This was shown for an array of phosphinic peptide inhibitors which were prepared by solid-phase peptide synthesis using a building block to introduce the phosphinic moiety.