Structure-Activity Relationship Study of Novel Peptoids That Mimic the Structure of Antimicrobial Peptides

Biljana Mojsoska, Ronald N. Zuckermann, Håvard Jenssen

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The constant emergence of new bacterial strains that resist the effectiveness of marketed antimicrobials has led to an urgent de-
mand for and intensive research on new classes of compounds to combat bacterial infections. Antimicrobial peptoids comprise
one group of potential candidates for antimicrobial drug development. The present study highlights a library of 22 cationic am-
phipathic peptoids designed to target bacteria. All the peptoids share an overall net charge of

4 and are 8 to 9 residues long;
however, the hydrophobicity and charge distribution along the abiotic backbone varied, thus allowing an examination of the
structure-activity relationship within the library. In addition, the toxicity profiles of all peptoids were assessed in human red
blood cells (hRBCs) and HeLa cells, revealing the low toxicity exerted by the majority of the peptoids. The structural optimiza-
tion also identified two peptoid candidates, 3 and 4, with high selectivity ratios of 4 to 32 and 8 to 64, respectively, and a concen-
tration-dependent bactericidal mode of action against Gram-negative
Escherichia coli
TidsskriftAntimicrobial Agents and Chemotherapy
Udgave nummer7
StatusUdgivet - 4 maj 2015

Bibliografisk note

This work was funded by The Danish Council for Independent Research(grant 10-085287).We also acknowledge the Molecular Foundry, whose work was sup-ported by the Office of Science, Office of Basic Energy Sciences, of the U.S.Department of Energy under contract DE-AC02-05CH11231.

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