DC Field | Value | Language |
---|---|---|
dc.contributor.author | Dong Hoon Oh | - |
dc.contributor.author | Song Yub Shin | - |
dc.contributor.author | Sang Won Lee | - |
dc.contributor.author | Joo Hyun Kang | - |
dc.contributor.author | Sun Don Kim | - |
dc.contributor.author | Pan Dong Ryu | - |
dc.contributor.author | Kyung Soo Hahm | - |
dc.contributor.author | Yang Mee Kim | - |
dc.date.accessioned | 2017-04-19T08:57:14Z | - |
dc.date.available | 2017-04-19T08:57:14Z | - |
dc.date.issued | 2000 | - |
dc.identifier.issn | 0006-2960 | - |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/5166 | - |
dc.description.abstract | A 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.publisher | Amer Chem Soc | - |
dc.title | 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 | - |
dc.title.alternative | 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 | - |
dc.type | Article | - |
dc.citation.title | Biochemistry | - |
dc.citation.number | 39 | - |
dc.citation.endPage | 11864 | - |
dc.citation.startPage | 11855 | - |
dc.citation.volume | 39 | - |
dc.contributor.affiliatedAuthor | Song Yub Shin | - |
dc.contributor.affiliatedAuthor | Joo Hyun Kang | - |
dc.contributor.affiliatedAuthor | Kyung Soo Hahm | - |
dc.contributor.alternativeName | 오동훈 | - |
dc.contributor.alternativeName | 신송엽 | - |
dc.contributor.alternativeName | 이상원 | - |
dc.contributor.alternativeName | 강주현 | - |
dc.contributor.alternativeName | 김선돈 | - |
dc.contributor.alternativeName | 유판동 | - |
dc.contributor.alternativeName | 함경수 | - |
dc.contributor.alternativeName | 김양미 | - |
dc.identifier.bibliographicCitation | Biochemistry, vol. 39, no. 39, pp. 11855-11864 | - |
dc.identifier.doi | 10.1021/bi000453g | - |
dc.description.journalClass | Y | - |
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