Insights into the Mechanism and Catalysis of Peptide Thioester Synthesis by Alkylselenols Provide a New Tool for Chemical Protein Synthesis

Florent Kerdraon (1) , Gemma Bogard (1) , Benoît Snella (1) , Hervé Drobecq (1) , Muriel Pichavant (1) , Vangelis Agouridas (1, 2) , Oleg Melnyk (1)

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

While thiol-based catalysts are widely employed for chemical protein synthesis relying on peptide thioester chemistry, this is less true for selenol-based catalysts whose development is in its infancy. In this study, we compared different selenols derived from the selenocysteamine scaffold for their capacity to promote thiol-thioester exchanges in water at mildly acidic pH and the production of peptide thioesters from bis(2-sulfanylethyl)amido (SEA) peptides. The usefulness of a selected selenol compound is illustrated by the total synthesis of a biologically active human chemotactic protein, which plays an important role in innate and adaptive immunity

Mots clés: Peptide thioester; alkylselenol; catalysis; chemical protein synthesis

Domaines: Chimie organique; Chimie thérapeutique; Catalyse

Florent Kerdraon, Gemma Bogard, Benoît Snella, Hervé Drobecq, Muriel Pichavant, et al.. Insights into the Mechanism and Catalysis of Peptide Thioester Synthesis by Alkylselenols Provide a New Tool for Chemical Protein Synthesis. Molecules, 2021, 26 (5), pp.1386. ⟨10.3390/molecules26051386⟩. ⟨hal-03139579v2⟩