Role of the hinge region and the tryptophan residue in the synthetic antimicrobial peptides, cecropin A(1-8)-magainin 2(1-12) and its analogues, on their antibiotic activities and structures

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dc.contributor.authorDong Hoon Oh-
dc.contributor.authorSong Yub Shin-
dc.contributor.authorSang Won Lee-
dc.contributor.authorJoo Hyun Kang-
dc.contributor.authorSun Don Kim-
dc.contributor.authorPan Dong Ryu-
dc.contributor.authorKyung Soo Hahm-
dc.contributor.authorYang Mee Kim-
dc.date.accessioned2017-04-19T08:57:14Z-
dc.date.available2017-04-19T08:57:14Z-
dc.date.issued2000-
dc.identifier.issn0006-2960-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/5166-
dc.description.abstractA 20-residue hybrid peptide CA(1-8)-MA(1-12) (CA-MA), incorporating residues 1-8 of cecropin A (CA) and residues 1-12 of magainin 2 (MA), has potent antimicrobial activity without toxicity against human erythrocytes. To investigate the effects of the Gly-Ile-Gly hinge sequence of CA-MA on the antibacterial and antitumor activities, two analogues in which the Gly-Ile-Gly sequence of CA-MA is either deleted (P1) or substituted with Pro (P2) were synthesized. The role of the tryptophan residue at position 2 of CA-MA on its antibiotic activity was also investigated using two analogues, in which the Trp2 residue of CA-MA is replaced with either Ala (P3) or Leu (P4). The tertiary structures of CA-MA, P2, and P4 in DPC micelles, as determined by NMR spectroscopy, have a short amphiphilic helix in the N-terminus and about three turns of α-helix in the C-terminus, with the flexible hinge region between them. The P1 analogue has an α-helix from Leu4 to Ala14 without any hinge structure. P1 has significantly decreased lytic activities against bacterial and tumor cells and PC/PS vesicles (3:1, w/w), and reduced pore-forming activity on lipid bilayers, while P2 retained effective lytic activities and pore-forming activity. The N-terminal region of P3 has a flexible structure without any specific secondary structure. The P3 modification caused a drastic decrease in the antibiotic activities, whereas P4, with the hydrophobic Leu side chain at position 2, retained its activities. On the basis of the tertiary structures, antibiotic activities, vesicle-disrupting activities, and pore-forming activities, the structure-function relationships can be summarized as follows. The partial insertion of the Trp2 of CA-MA into the membrane, as well as the electrostatic interactions between the positively charged Lys residues at the N-terminus of the CA-MA and the anionic phospholipid headgroups, leads to the primary binding to the cell membrane. Then, the flexibility or bending potential induced by the Gly-Ile-Gly hinge sequence or the Pro residue in the central part of the peptides may allow the α-helix in the C-terminus to span the lipid bilayer. These structural features are crucial for the potent antibiotic activities of CA-MA.-
dc.publisherAmer Chem Soc-
dc.titleRole of the hinge region and the tryptophan residue in the synthetic antimicrobial peptides, cecropin A(1-8)-magainin 2(1-12) and its analogues, on their antibiotic activities and structures-
dc.title.alternativeRole of the hinge region and the tryptophan residue in the synthetic antimicrobial peptides, cecropin A(1-8)-magainin 2(1-12) and its analogues, on their antibiotic activities and structures-
dc.typeArticle-
dc.citation.titleBiochemistry-
dc.citation.number39-
dc.citation.endPage11864-
dc.citation.startPage11855-
dc.citation.volume39-
dc.contributor.affiliatedAuthorSong Yub Shin-
dc.contributor.affiliatedAuthorJoo Hyun Kang-
dc.contributor.affiliatedAuthorKyung Soo Hahm-
dc.contributor.alternativeName오동훈-
dc.contributor.alternativeName신송엽-
dc.contributor.alternativeName이상원-
dc.contributor.alternativeName강주현-
dc.contributor.alternativeName김선돈-
dc.contributor.alternativeName유판동-
dc.contributor.alternativeName함경수-
dc.contributor.alternativeName김양미-
dc.identifier.bibliographicCitationBiochemistry, vol. 39, no. 39, pp. 11855-11864-
dc.identifier.doi10.1021/bi000453g-
dc.description.journalClassY-
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