Covalent Labeling of Matrix Metalloproteases with Affinity-Based Probes Containing Tuned Reactive N-Acyl-N-Alkyl Sulfonamide Cleavable Linkers.

Original covalent probes with an N-acyl-N-alkyl sulfonamide cleavable linker were developed to target a broad set of human Matrix Metalloproteases (MMPs). The electrophilicity of this cleavable linker was modulated to improve the selectivity of the probes as well as reduce their unspecific reactivity in complex biological matrices. We first demonstrated that targeting the S subsite of MMPs enables access to broad-spectrum affinity-based probes that exclusively react with the active version of these proteases.

Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions.

In this report, a synthetic protocol for the preparation of phosphinic dipeptides of type is presented. These compounds serve as valuable building blocks for the development of highly potent phosphinopeptidic inhibitors of medicinally relevant Zn-metalloproteases and aspartyl proteases. The proposed method is based on the tandem esterification of α-aminophosphinic and acrylic acids under silylating conditions in order to subsequently participate in a -Michael reaction.