NMR based structure-activity relationship analysis of an antimicrobial peptide, thanatin, engineered by site-specific chemical modification: Activity improvement and spectrum alteration.
Activity improvement of an antimicrobial peptide, thanatin, has been achieved up to 4-fold higher than natural original one by site-specific chemical modifications with tert-butyl group at two cysteine residues which form an intramoleular disulfide bridge. The chemically modified thanatin (C11tBu/C18tBu) exhibited improved antimicrobial activity toward Gram-positive bacteria, Micrococcus luteus, whereas lowered activity toward Gram-negative bacteria, Escherichia coli. This finding suggests that disulfide-bridge formation is not only indispensable for exhibition of antimicrobial activity of thanatin but also closely related to the activity specificity towards bacteria. NMR analysis indicates that thanatin acts against E.coli stereospecifically by taking advantage of its C-terminal beta-hairpin structure, while the activity against M. luteus does not relate to structures and correlates very well to side-chain hydrophobicity.
Imamura
Tomohiro
T
Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.
Yamamoto
Naoki
N
Tamura
Atsuo
A
Murabayashi
Shinji
S
Hashimoto
Shigeki
S
Shimada
Hiroaki
H
Taguchi
Seiichi
S
D019943:Amino Acid Substitution; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D010456:Peptides, Cyclic; C098076:thanatin