title: NMR structural characterization of cecropin A(1-8) - magainin 2(1-12) and cecropin A (1-8) - melittin (1-12) hybrid peptides.
abstract: In order to elucidate the structure-antibiotic activity relationships of the peptides, the three-dimensional structures of two hybrid peptides, CA(1-8) - MA(1-12) and CA(1-8) - ME(1-12) in trifluoroethanol-containing aqueous solution were investigated by NMR spectroscopy. Both CA(1-8) - MA(1-12) and CA(1-8) - ME(1-12) have strong antibacterial activity but only CA(1-8) - ME(1-12) has hemolytic activity against human erythrocytes. CA(1-8) - MA(1-12) has a hydrophobic 310-helix of only two turns combined with one short helix in the N-terminus with a flexible hinge section in between. CA(1-8) - MA(1-12) has a severely bent structure in the middle of the peptide. These structural features as well as the low hydrophobicity of CA(1-8) - MA(1-12) seem to be crucial for the selective lysis against the membrane of prokaryotic cells. CA(1-8) - ME(1-12) has an alpha-helical structure of about three turns in the melittin domain and a flexible structure with one turn in the cecropin domain connected with a flexible hinge section in between, and these might be the structural features required for membrane disruption against prokaryotic and eukaryotic cells. The central hinge region (Gly9-Ile10-Gly11) in an amphipathic antibacterial peptide is considered to play an important role in providing the conformational flexibility required for ion channel formation of the C-terminal hydrophobic alpha-helix on cell membrane.
authors.affiliation: Department of Chemistry, Konkuk University, Seoul, Korea.
authors.forename: D
authors.initials: D
authors.lastname: Oh
authors.forename: S Y
authors.initials: SY
authors.lastname: Shin
authors.forename: J H
authors.initials: JH
authors.lastname: Kang
authors.forename: K S
authors.initials: KS
authors.lastname: Hahm
authors.forename: K L
authors.initials: KL
authors.lastname: Kim
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D018288:Carcinoma, Small Cell / Q000473:pathology; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008555:Melitten / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006460:Hemolysin Proteins; D010455:Peptides; C121751:cecropin A(1-8)magainin 2(1-12); C121750:cecropin A(1-8)melittin(1-2); D008555:Melitten