Ahn, M., Murugan, R.N., Nan, Y.H., Cheong, C., Sohn, H., Kim, E.H., Hwang, E., Ryu, E.K., Kang, S.W., Shin, S.Y., Bang, J.K. (2011). Substitution of the GalNAc-α-O-Thr¹¹ residue in drosocin with O-linked glyco-peptoid residue: effect on antibacterial activity and conformational change.  Bioorg. Med. Chem. Lett. 21(20): 6148--6153.

FBrf0217186

Research paper

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 Thr(11) residue. One of our glyco-peptoid analogues showed an increased antibacterial activity by the modification of the Thr(11) 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 Thr(11) residue derivative and (S)-configuration over (R)-configuration.