Structure-activity relationship study of the antimicrobial CRAMP-derived peptide CRAMP20-33

We report here on the structure-activity relationship study of a 14 amino acid fragment of the cathelicidin-related antimicrobial peptide (CRAMP), CRAMP20-33 (KKIGQKIKNFFQKL). It showed activity against Escherichia coli and filamentous fungi with IC50 values below 30 μM and 10 μM, respectively. CRAMP20-33 variants with glycine at position 23 substituted by phenylalanine, leucine or tryptophan showed 2- to 4-fold improved activity against E. coli but not against filamentous fungi. Furthermore, the most active single-substituted peptide, CRAMP20-33 G23 W (IC50 = 2.3 μM against E. coli), showed broad-spectrum activity against Candida albicans, Staphylococcus epidermidis and Salmonella Typhimurium. Introduction of additional arginine substitutions in CRAMP20-33 G23 W, more specifically in CRAMP20-33 G23 W N28R or CRAMP20-33 G23 W Q31R, resulted in 3-fold increased activity against S. epidermidis (IC50 = 4 μM and 4.8 μM, respectively) as compared to CRAMP20-33 G23 W (IC50 = 15.1 μM) but not against the other pathogens tested. In general, double-substituted variants were non-toxic for human HepG2 cells, pointing to their therapeutic potential.

Publication year:2018

BOF-keylabel:yes

IOF-keylabel:yes

BOF-publication weight:1

CSS-citation score:1

Authors from:Government, Higher Education

Accessibility:Open