[4,4′‐(Z)‐Dehydrophenylalanine]gramicidin S with stabilized bioactive conformation and strong antimicrobial activity

Open Access
Publisher Website
Google Scholar
Abstract
Dehydrophenylalanine (ΔPhe) was incorporated into an antibiotic peptide gramicidin S (GS) in place of D‐Phe4,4′ to prepare an unsaturated analog. Conformational analysis with 1H‐NMR indicated that the unsaturated analog has much the same backbone conformation as that of natural gramicidin S as shown by NOE experiments. Studies on temperature dependences and on the chemical shift differences showed that the hydrogen bonds between Val‐NH and Leu‐CO in the unsaturated analog are strengthened by the incorporation of ΔPhe4,4′. This resulted in the reinforcement of the β‐sheet structure which is the most important structural element for GS bioactivity. [ΔPhe4,4′]gramicidin S exhibited indeed very strong antimicrobial activities against Gram‐positive bacteria as well as the natural peptide.