Substitution of the GalNAc-α-O-Thr11 residue in drosocin with O-linked glyco-peptoid residue: Effect on antibacterial activity and conformational change

One of the obvious disadvantages of natural peptides is their liability to proteases. Among the several solutions for this issue, peptoids or oligomers of N-substituted glycine have emerged as a promising tool that may enhance the stability of proteolysis-susceptible natural peptides. We have synthesized the drosocin and its glyco-peptoid analogues linked O-GalNAc at the Thr11 residue. One of our glyco-peptoid analogues showed an increased antibacterial activity by the modification of the Thr11 residue with glyco-peptoid. Structure–activity relationship studies revealed that the antibacterial activity by glyco-peptoid drosocin requires three key elements: free hydroxyl group on the carbohydrate moiety, γ-methyl group of the Thr11 residue derivative and (S)-configuration over (R)-configuration.

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