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

Paul Geurink, Theo Klein, Michiel Leeuwenburgh, Gijs van der Marel, Henk Kauffman, Rainer Bischoff*, Herman Overkleeft

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)1244-1250
Number of pages7
JournalOrganic and Biomolecular Chemistry
Volume6
Issue number7
DOIs
Publication statusPublished - 22-Feb-2008

Keywords

  • SOLID-PHASE SYNTHESIS
  • NECROSIS-FACTOR-ALPHA
  • MATRIX METALLOPROTEINASES
  • CONVERTING-ENZYME
  • INHIBITORS
  • ACIDS
  • DESIGN
  • RESIN
  • MARIMASTAT
  • PROTEINS

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