A peptidehydroxamate library for enrichment of metalloproteinases: towards an affinity-based metalloproteinase profiling protocol

Abstract

A compound library of 96 enantiopure N-terminal succinyl hydroxamate functionalized peptides was synthesized on solid phase. All compounds were tested for their inhibitory potential towards MMP-9, MMP-12 and ADAM-17, which led to the identification of both broad spectrum inhibitors and metalloproteinase-selective ones. Eight potent and less potent inhibitors were immobilized on Sepharose beads and evaluated in solid-phase enrichment of active MMP-9, MMP-12 and ADAM-17. In addition, one of these inhibitors was used for solid-phase enrichment of endogenous ADAM-17 from a complex proteome (a lysate prepared from cultured A549 cells).