Dissecting MMP P₁₀' and P₁₁' subsite sequence preferences, utilizing a positional scanning, combinatorial triple-helical peptide library.

ABSTRACT: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that remodel the extracellular matrix environment and mitigate outside-in signaling. Loss of regulation of MMP activity plays a role in numerous pathological states. In particular, aberrant collagenolysis affects tumor invasion and metastasis, osteoarthritis, and cardiovascular and neurodegenerative diseases. To evaluate the collagen sequence preferences of MMPs, a positional scanning synthetic combinatorial library was synthesized herein and was used to investigate the P₁₀' and P₁₁' substrate subsites. The scaffold for the library was a triple-helical peptide mimic of the MMP cleavage site in types I-III collagen. A FRET-based enzyme activity assay was used to evaluate the sequence prefere

SUBMITTER: Tokmina-Roszyk M 

PROVIDER: S-EPMC6204916 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature