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Design of Peptide Hydroxamate‐Based Photoreactive Activity‐Based Probes of Zinc‐Dependent Metalloproteases
Author(s) -
Geurink Paul P.,
Klein Theo,
Prèly Laurette,
Paal Krisztina,
Leeuwenburgh Michiel A.,
van der Marel Gijs A.,
Kauffman Henk F.,
Overkleeft Herman S.,
Bischoff Rainer
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200901385
Subject(s) - chemistry , metalloproteinase , matrix metalloproteinase , extracellular matrix , peptide , cell , biochemistry , extracellular , zinc , cell growth , matrix metalloproteinase 3 , microbiology and biotechnology , biophysics , biology , organic chemistry
Metalloproteases (ADAMs, MMPs) are multidomain proteins that play key roles in extracellular matrix remodelling and degradation, in cell–cell and cell–matrix interactions and in the proteolytic liberation of membrane‐anchored proforms of cytokines and growth factors, the so‐called ectodomainshedding. In this work we describe the development ofphotoactivatable activity‐based probes with which active metalloproteases can be visualised. Our probes are based on the succinyl hydroxamate motif and differ in the positioning of the trifluoromethylphenyldiazirine photoreactive group. We demonstrate that directing the photoactivatable group towards the S1′ pocket yields activity‐based probes more effective than the corresponding probe with the photoactivatable group directed towards the S2′ pocket.