[4,4'-(Z)-dehydrophenylalanine]gramicidin S with stabilized bioactive conformation and strong antimicrobial activity.
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.
D002942:Circular Dichroism; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006096:Gramicidin / Q000138:chemical synthesis* / Q000494:pharmacology / Q000031:analogs & derivatives; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013696:Temperature
C053862:(4,4'-dehydrophenylalanine)gramicidin S; D006096:Gramicidin