Activity-based probes enable discrimination between the active enzyme and its inactive or inactivated counterparts.S ince metalloproteases catalysis is non-covalent, activity-based probes targeting them have been systematically developed by decorating reversible inhibitors with photocrosslinkers.Byexploiting two types of ligand-guided chemistry,w ei dentified novel activity-based probes capable of covalently modifying the active site of matrix metalloproteases (MMPs) without any external trigger.T he 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,a t0 .07 %( w/w)) in complex proteomes.F inally,t his ligand-directed chemistry was successfully applied to label active MMP-12 secreted by eukaryote cells.Webelieve that this approach could be transferred more widely to many other metalloproteases,t hus contributing to tackle their unresolved proteomic profiling in vivo.

We report the use of air-stable Cu­(I)-NHC complex 4a as a catalyst for the efficient microwave-assisted synthesis of peptidotriazoles on solid phase. Compared with the usual conditions (CuI or CuSO4/NaAsc), catalyst 4a allowed the preparation of a series of peptidomimetic compounds containing a 1,2,3-triazole ring in their backbone without the oxidation of common side-chains. Overall, the peptidotriazoles were obtained in good yields (61–87%), in excellent purity (higher than 94%) and with low copper contamination.

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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.

Among non-covalent bonds, the host-guest interaction is an attractive way to attach biomolecules to solid surfaces since the binding strength can be tuned by the nature of host and guest partners or through the valency of the interaction. For that purpose, we synthesized cyclodecapeptide scaffolds exhibiting in a spatially controlled manner two independent domains enabling the multimeric presentation of guest molecules on one face and the other face enabling the potential grafting of a biomolecule of interest. In this work, we were interested in the β-cyclodextrin/ferrocene inclusion complex formed on β-CD monolayers functionalized surfaces. By using surface sensitive techniques such as quartz crystal microbalance and surface plasmon resonance, we quantified the influence of the guest valency on the stability of the inclusion complexes. The results show a drastic enhancement of the affinity with the gradual increase of guest valency. Considering that the sequential binding events are equal and independent, we applied the multivalent model developed by the Huskens group to extract intrinsic binding constants and an effective concentration of host.

A method for regioselective solid‐phase synthesis of disubstituted peptidoisoxazoles is reported. Improved conditions for the synthesis of 3,5‐disubstituted isoxazoles (mimicking s‐trans peptide bond) without metal catalysts were implemented. New conditions enabling the synthesis of 3,4‐disubstituted isoxazoles (mimicking s‐cis peptide bond) using ruthenium catalysts were developed. This study provides a means for the regioselective preparation of new libraries of peptidomimetic molecules containing an isoxazole moiety within the backbone.