Solution structure of a designed amphipathic antimicrobial synthetic peptide, PGAa

A designed peptide, PGAa showed an excellent antifungal activity as well as an efficient bactericidal activity toward gram-positive, especially in the pathogenic yeast Candida albicans 28838. The solution structures of PGAa h ave been determined both in 40% TFE/water solution and DPC micelle by CD an d NMR spectroscopy. Based on NOEs, vicinal coupling constants? backbone ami de exchange rates, and chemical shift indices, PGAa formed a long amphipath ic cu-helical conformation in both TFE and DPC micelle environments, spanni ng the residues Ile(2)-Ala(19) in TFE and Lys(5)-Ala(19) in DPC micelle, re spectively. Solution structures suggested that the hydrophobic residues wou ld interact with the fatty acyl chains of the Lipid bilayer, while the posi tively charged side-chains exposed to aqueous environments. Therefore, we c onclude that the alpha-helical structure as well as the highly amphiphatic nature of PGAa peptide may play a critical role in its antimicrobial activi ty as well as selectivities in different species. (C) 2000 Academic Press.