Antibiotic resistance has been a rising problem worldwide over the past several years. Both fungi and bacteria are quickly developing mutations to render antibiotics useless. There have been many studies to find therapeutic alternatives to conventional antibiotics, such as antimicrobial peptides (AMPs) and N-alkylated peptidomimetics, known as peptoids. Peptoids have proven to be useful antibiotic alternatives due to their broad-spectrum activity against bacteria and fungi, non-specific mode of action, decreased susceptibility to enzymatic degradation, and long half-lives <i>in vivo</i>. Here we will report our exploration into ways to modify peptoid structure to improve antimicrobial activity and reduce cytotoxicity. Peptoids were optimized through changes in side-chain functionality, length, and/or charge. The effect of these modifications on biological activity was done through minimum inhibitory concentration testing against several bacteria and fungi as well as cytotoxicity testing against mammalian cells.

Modification of peptoid length and side-chain functionality to improve biological activity

ACS Spring 2022

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