engleski

Design of PGLa-H tandem-repeat peptides with activity and selectivity testing against clinical bacterial isolates

Antimicrobial peptides (AMPs) are promising candidates for new classes of antibiotics but tend to display an inacceptable toxicity to human cells. A naturally produced C-terminal fragment of PGLa, named PGLa-H, was reported to have a very low haemolytic activity with a moderate antibacterial activity. We designed of sequential tandem repeat of PGLa-H and its analogue with glycine substitution at key position. DiPGLa-H and its analogue showed markedly improved in vitro bacteriostatic and bactericidal activity against laboratory strains and multidrug resistant clinical isolates of both Gram-negative and Gram-positive pathogens. At the same time they were non-toxic for circulating human blood cells as assessed by geno/cytotoxicity and haemolysis assays. An analogue with a single glycine substitution showed a slightly better antibacterial activity and somewhat reduced cytotoxicity. In the future these peptides may serve as useful lead compounds for developing non-toxic anti-infective agents against multi-resistant pathogens, especially for topical uses.

Antimicrobial peptides ; PGLa-H ; Clinical isolates ; Multidrug resistant ; Cytoxicity

nije evidentirano