Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine

Nathalie Ollivier (1) , Vangelis Agouridas (1) , Benoît Snella (1) , Rémi Desmet (1) , Hervé Drobecq (1) , Jérôme Vicogne (1) , Oleg Melnyk (1)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204

Hydrazone and oxime peptide ligations are catalyzed by arginine. The catalysis is assisted intramolecularly by the side-chain guanidinium group. Hydrazone ligation in the presence of arginine proceeds efficiently in phosphate buffer at neutral pH but is particularly powerful in bicarbonate/CO2 buffer. In addition to acting as a catalyst, arginine prevents the aggregation of proteins during ligation. With its dual properties as a nucleophilic catalyst and a protein aggregation inhibitor, arginine hydrochloride is a useful addition to the hydrazone/oxime ligation toolbox.

Domaines: Chimie organique; Catalyse

Nathalie Ollivier, Vangelis Agouridas, Benoît Snella, Rémi Desmet, Hervé Drobecq, et al.. Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine. Organic Letters, 2020, 22 (21), pp.8608-8612. ⟨10.1021/acs.orglett.0c03195⟩. ⟨hal-02995245⟩