Thiocarbamate-linked peptides by chemoselective peptide ligation.
Peptide chemical ligation chemistries, which allow the chemoselective coupling of unprotected peptide fragments, are useful tools for synthesizing native polypeptides or unnatural peptide-based macromolecules. We show here that the phenylthiocarbonyl group can be easily introduced into peptides on alpha or epsilon amino groups using phenylthiochloroformate and standard solid-phase method. It reacts chemoselectively with cysteinyl peptides to give an alkylthiocarbamate bond. S,N-shift of the alkylaminocarbonyl group from the Cys side chain to the alpha-amino group did not occur. The method was used for linking two peptide chains through their N-termini, for the synthesis of a cyclic peptide or for the synthesis of di- or tetravalent multiple antigenic peptides (MAPs). Thiocarbamate ligation is thus complementary to thioether, thioester or disulfide ligation methods.
Besret
Soizic
S
UMR 8161 CNRS-Université de Lille 1 et 2, Institut Pasteur de Lille, IFR 142, 1 rue du Pr Calmette, 59021, Lille, France.
Ollivier
Nathalie
N
Blanpain
Annick
A
Melnyk
Oleg
O