Đang chuẩn bị liên kết để tải về tài liệu:
Báo cáo khoa học: Effects of a tryptophanyl substitution on the structure and antimicrobial activity of C-terminally truncated gaegurin 4

Gaegurin 4 (GGN4), a 37-residue antimicrobial peptide, consists of two amphipathic ahelices (residues 2–10and 16–32) connected by a flexible loop region (residues 11– 15). As part of an effort to develop new peptide antibiotics with low molecular mass, the activities of C-terminally truncated GGN4 analogues were tested. D 24)37 GGN4, a peptide analogue with 14 residues truncated from the C-terminus of GGN4, showed a complete loss of anti-microbial activity. | Eur. J. Biochem. 269 4367-4374 2002 FEBS 2002 doi 10.1046 j.1432-1033.2002.03139.x Effects of a tryptophanyl substitution on the structure and antimicrobial activity of C-terminally truncated gaegurin 4 Hyung-Sik Won1 Sang-Ho Park1 Hyung Eun Kim1 Byongkuk Hyun2 Mijin Kim2 Byeong Jae Lee2 and Bong-Jin Lee1 1 College of Pharmacy Seoul National University Seoul South Korea 2Institute of Molecular Biology and Genetics Seoul National University Seoul South Korea Gaegurin 4 GGN4 a 37-residue antimicrobial peptide consists of two amphipathic a helices residues 2-10 add 16-32 connected by a flexible loop region residues 1115 . As part of an effort to develop new peptide antibiotics with low molecular mass the activities of C-terminally truncated GGN4 analogues were tested. A24-37 GGN4 a peptide analogue with 14 residues truncated from the C-terminus of GGN4 showed a complete loss of antimicrobial activity. However the single substitution of aspartic acid 16 by tryptophan D16W in the A24-37 GGN4 completely restored the antimicrobial activity without any significant hemolytic activity. In contrast neither the D16F nor K15W substitution of the A24-37 GGN4 allowed such a dramatic recovery of activity. In addition the D16W substitution of the native GGN4 significantly enhanced the hemolytic activity as well as the antimicrobial activity. The structural effect of the D16W substitution in the A24-37 GGN4 was investigated by CD NMR and fluorescence spectroscopy. The results showed that the single tryptophanyl substitution at position 16 of the A24-37 GGN4 induced an a helical conformation in the previously flexible loop region in intact GGN4 thereby forming an entirely amphipathic a helix. In addition the substituted tryptophan itself plays an important role in the membrane-interaction of the peptide. Keywords antimicrobial peptide GGN4 analogues tryptophanyl substitution CD NMR. Membrane-active peptides exhibit many interesting biological and pharmacological activities and they .