Shimohigashi Y, Kodama H, Imazu S, Horimoto H, Sakaguchi K, Waki M, Uchida H, Kondo M, Kato T, Izumiya N
Laboratory of Biochemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
FEBS Lett. 1987 Oct 5;222(2):251-5. doi: 10.1016/0014-5793(87)80380-0.
Dehydrophenylalanine (delta Phe) 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 delta Phe4,4'. This resulted in the reinforcement of the beta-sheet structure which is the most important structural element for GS bioactivity. [delta Phe4,4']gramicidin S exhibited indeed very strong antimicrobial activities against Gram-positive bacteria as well as the natural peptide.
