Insights into the Mechanism and Catalysis of Peptide Thioester Synthesis by Alkylselenols Provide a New Tool for Chemical Protein Synthesis
Florent Kerdraon,
Gemma Bogard,
Benoît Snella,
Hervé Drobecq,
Muriel Pichavant,
Vangelis Agouridas,
Oleg Melnyk
Affiliations
Florent Kerdraon
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
Gemma Bogard
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
Benoît Snella
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
Hervé Drobecq
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
Muriel Pichavant
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
Vangelis Agouridas
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
Oleg Melnyk
U1019-UMR 9017—CIIL—Center for Infection and Immunity of Lille, Institut Pasteur de Lille, University of Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France
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.
