Wednesday, April 24, 2019

Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation

Shang Jia, Dan He, and Christopher J. Chang

Journal of the American Chemical Society, 2019

Site-selective bioconjugation to native protein residues is a powerful tool for protein functionalization, with cysteine and lysine side chains being the most common points for attachment owing to their high nucleophilicity. We now report a strategy for histidine modification using thiophosphorodichloridate reagents that mimic post-translational histidine phosphorylation, enabling fast and selective labeling of protein histidines under mild conditions where various payloads can be introduced via copper-assisted alkyne–azide cycloaddition (CuAAC) chemistry. We establish that these reagents are particularly effective at covalent modification of His-tags, which are common motifs to facilitate protein purification, as illustrated by selective attachment of polyarginine cargoes to enhance the uptake of proteins into living cells. This work provides a starting point for probing and enhancing protein function using histidine-directed chemistry.

Restricted Rotational Flexibility of the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase

Nichole K. Stewart, Marta Toth, Pojun Quan, Michael Beer, John D. Buynak, Clyde A. Smith, and Sergei B. Vakulenko ACS Infectious Diseases   ...