Structure-function-guided design of synthetic peptides with anti-infective activity derived from wasp venom.

ABSTRACT: Antimicrobial peptides (AMPs) derived from natural toxins and venoms offer a promising alternative source of antibiotics. Here, through structure-function-guided design, we convert two natural AMPs derived from the venom of the solitary eumenine wasp Eumenes micado into α-helical AMPs with reduced toxicity that kill Gram-negative bacteria in vitro and in a preclinical mouse model. To identify the sequence determinants conferring antimicrobial activity, an alanine scan screen and strategic single lysine substitutions are made to the amino acid sequence of these natural peptides. These efforts yield a total of 34 synthetic derivatives, including alanine substituted and lysine-substituted sequences with stabilized α-helical structures and increased net positive charge. The resul

SUBMITTER: Boaro A 

PROVIDER: S-EPMC10795512 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature