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Article Dans Une Revue Angewandte Chemie International Edition Année : 2021

Ligand‐directed modification of active matrix metalloproteases: activity‐based probes with no photolabile group

Isabelle Correia
Dimitris Georgiadis
Olivier Lequin

Résumé

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 S$_3$′ 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.

Domaines

Chimie
Kaminska manuscript.docx (20.55 Mo) Télécharger le fichier

Dates et versions

hal-03965993 , version 2 (31-01-2023)
hal-03965993 , version 1 (10-02-2023)

Identifiants

Citer

Monika Kaminska, Pierrick Bruyat, Carole Malgorn, Marion Doladilhe, Evelyne Cassar-Lajeunesse, et al.. Ligand‐directed modification of active matrix metalloproteases: activity‐based probes with no photolabile group. Angewandte Chemie International Edition, 2021, 60 (33), pp.18272-18279. ⟨10.1002/anie.202106117⟩. ⟨hal-03965993v2⟩
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