Design and Characterization of a Metalloproteinase Inhibitor-Tethered Resin for the Detection of Active MMPs in Biological Samples

Dusan Hesek, Marta Toth, Samy O. Meroueh, Stephen Brown, Huiren Zhao, Wael Sakr, Rafael Fridman, Shahriar Mobashery

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Matrix metalloproteinases (MMPs), zinc-dependent endopeptidases, are implicated in tumor progression. We describe herein the development of a resin-immobilized, broad-spectrum synthetic MMP inhibitor for selective binding of the active forms of MMPs from different experimental samples. We confirmed the activity-based binding of MMPs to the inhibitor-tethered resin with purified human recombinant MMP-2, -9, and -14, samples of cultured cells, and tissue extracts. Our results show that only the free active MMPs, and not the zymogens or MMP/TIMP (enzyme-protein inhibitor) complexes, bound specifically to the resin. In our comparison of benign and carcinoma tissue extracts, we detected active MMP-2 and MMP-14 forms only in the cancerous tissue samples, indicating that a pool of the tumor MMPs is free of endogenous inhibitors (TIMPs), and is thus likely to contribute to proteolytic events that precipitate tumor metastasis.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalChemistry and Biology
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

Keywords

  • CELLCYCLE
  • CHEMBIO

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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