6. C-Terminal Modifications Broaden Activity of the Proline-Rich Antimicrobial Peptide, Chex1-Arg20

Abstract:

A series of N- and C-terminal modifications of the monomeric proline-rich antimicrobial peptide, Chex1-Arg20, was obtained via different chemical strategies using Fmoc/tBu solid-phase peptide synthesis in order to study their effects on a panel of Gram-negative bacteria. In particular, C-terminal modifications with hydrazide or alcohol functions extended their antibacterial activity from E. coli and K. pneumoniae to other Gram-negative species, A. baumannii and P. aeruginosa. Furthermore, these analogues did not show cytotoxicity towards mammalian cells. Hence, such modifications may aid in the development of more potent proline-rich antimicrobial peptides with a greater spectrum of activity against Gram-negative bacteria than the parent peptide.

Li, W.; Tailhades, J.; Hossain, M. A.; O’Brien-Simpson, N. M.; Reynolds, E. C.; Otvos, L.; Separovic, F.; Wade, J. D.* (2015): C-Terminal modifications broaden activity of the proline-rich antimicrobial peptide, Chex1-Arg20. Aust. J. Chem. 68, 1373-1378, DOI: 10.1071/CH15169