Premium
[4,4′‐( Z )‐Dehydrophenylalanine]gramicidin S with stabilized bioactive conformation and strong antimicrobial activity
Author(s) -
Shimohigashi Yasuyuki,
Kodama Hiroaki,
Imazu Sachiko,
Horimoto Hideaki,
Sakaguchi Kazuyasu,
Waki Michinori,
Uchida Hiroaki,
Kondo Michio,
Kato Tetsuo,
Izumiya Nobuo
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80380-0
Subject(s) - antimicrobial , gramicidin s , chemistry , gramicidin , stereochemistry , biochemistry , organic chemistry , membrane
Dehydrophenylalanine (ΔPhe) was incorporated into an antibiotic peptide gramicidin S (GS) in place of D‐Phe 4,4′ to prepare an unsaturated analog. Conformational analysis with 1 H‐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 ΔPhe 4,4′ . This resulted in the reinforcement of the β‐sheet structure which is the most important structural element for GS bioactivity. [ΔPhe 4,4′ ]gramicidin S exhibited indeed very strong antimicrobial activities against Gram‐positive bacteria as well as the natural peptide.