Ligand-Directed Modification of Active Matrix Metalloproteases: Activity-based Probes with no Photolabile Group.

Angewandte Chemie
Monika KaminskaLaurent Devel

Abstract

Activity-based probes enable discrimination between the active enzyme and its inactive or inactivated counterparts. Since metalloproteases catalysis is non-covalent, activity-based probes targeting them have been systematically developed by decorating reversible inhibitors with photo-crosslinkers. By exploiting two types of ligand-guided chemistry, we identified novel activity-based probes capable of covalently modifying the active site of matrix metalloproteases (MMPs) without any external trigger. The ability of these probes to label recombinant MMPs was validated in vitro and the identity of the main labelling sites within their S3 ' region unambiguously assigned. We also demonstrated that our affinity probes can react with rhMMP12 at nanogram scale (that is, at 0.07 % (w/w)) in complex proteomes. Finally, this ligand-directed chemistry was successfully applied to label active MMP-12 secreted by eukaryote cells. We believe that this approach could be transferred more widely to many other metalloproteases, thus contributing to tackle their unresolved proteomic profiling in vivo.

References

Mar 30, 2002·Science·Lisa M CoussensLynn M Matrisian
Jun 25, 2004·Chemical Communications : Chem Comm·Qing ZhuShao Q Yao
Jun 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alan SaghatelianBenjamin F Cravatt
Nov 4, 2004·Journal of the American Chemical Society·Elaine W S ChanShao Q Yao
Feb 17, 2006·The Journal of Biological Chemistry·Laurent DevelVincent Dive
Mar 28, 2006·Nature Chemical Biology·Stephan A SieberBenjamin F Cravatt
Apr 7, 2006·Organic Letters·Michiel A LeeuwenburghHerman S Overkleeft
Aug 11, 2006·Organic Letters·Jun WangShao Q Yao
May 10, 2008·Cancer Metastasis Reviews·Randy L SchererLynn M Matrisian
Oct 8, 2009·Chemical Biology & Drug Design·Christopher ForbesShahriar Mobashery
Apr 5, 2011·Theranostics·Lei ZhuXiaoyuan Chen
Oct 27, 2011·Topics in Current Chemistry·Paul P GeurinkHerman S Overkleeft
Jan 6, 2012·Nature Structural & Molecular Biology·Edgar DeuMatthew Bogyo
Feb 23, 2012·Journal of the American Chemical Society·Sho-hei FujishimaItaru Hamachi
Mar 21, 2012·ChemMedChem·Sevnur SerimSteven H L Verhelst
Dec 4, 2012·Chembiochem : a European Journal of Chemical Biology·Catherine NuryVincent Dive
Dec 29, 2012·The Journal of Biological Chemistry·Catherine NuryVincent Dive
May 25, 2013·Journal of the American Chemical Society·Montse MorellMatthew Bogyo
May 3, 2014·Nature Medicine·David J MarchantChristopher M Overall
Jun 20, 2014·Bioconjugate Chemistry·Lianne I WillemsSander I van Kasteren
Nov 8, 2014·Nature Reviews. Drug Discovery·Roosmarijn E Vandenbroucke, Claude Libert
May 12, 2015·Biochimica Et Biophysica Acta·Martijn Verdoes, Steven H L Verhelst
Aug 16, 2016·Nature Chemical Biology·Kei YamauraItaru Hamachi
Oct 26, 2016·Methods in Molecular Biology·Laurette PrelyRainer Bischoff
Apr 8, 2017·Nature Communications·Sho WakayamaItaru Hamachi
May 21, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Parker G JobinChristopher M Overall
Oct 24, 2017·ACS Medicinal Chemistry Letters·Sebastián A TesteroShahriar Mobashery
Aug 12, 2018·Trends in Biochemical Sciences·Matej VizovišekBoris Turk
Dec 29, 2018·Journal of the American Chemical Society·Tomonori Tamura, Itaru Hamachi
May 3, 2020·Cells·Helena Laronha, Jorge Caldeira

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