In by admin

Name Mr. Benjamin Rathman
Organization or Institution University of South Florida
Presentation Type Poster
Topic Organic Chemistry

Backbone Aminated Gramicidin S Analogues with Enhanced Antimicrobial Activity


Benjamin M. Rathman, Jessie Adams, Lindsey N. Shaw, and Juan R. Del Valle

Author Institution(s)

University of South Florida


Gramicidin S (GS) is a naturally occurring β-sheet-like cyclic decapeptide from Bacillus brevis that possesses antimicrobial activity against gram-positive and gram-negative bacteria. While GS is very potent it also causes hemolysis of human erythrocytes; therefore significant effort has been devoted to improving its selectivity for bacterial over mammalian cells. Recently our lab has shown peptide backbone N-amination stabilizes β-sheet folds. This modification could be applied to GS analogues that retain a bioactive confirmation. Here we report the synthesis and biological evaluation of N-aminated analogues of GS. Their antimicrobial activity was assayed against a panel of drug-resistant gram-positive and gram-negative bacteria known as ESKAPE pathogens, and their cytotoxicity measured using human red blood cells. Several N-aminated analogues not only showed improved antimicrobial activity but also reduced hemolytic activity. We believe the improved selectivity is due to the increased stabilization of the β-Sheet that N-amination affords.