title: Structural determinants for the membrane interaction of novel bioactive undecapeptides derived from gaegurin 5.
abstract: Gaegurin 5 is a 24-residue, membrane-active antimicrobial peptide isolated from the skin of an Asian frog, Rana rugosa. We recently reported the antimicrobial activities of two novel undecapeptides derived from an inactive N-terminal fragment (residues 1-11) of gaegurin 5 (Won, et al. J. Biol. Chem. 2004, 279, 14784-14791). In the present work, the anticancer activities of the two antimicrobial undecapeptide analogues were additionally identified. The relationships between their structural properties and biological activities were assessed by characterizing the fundamental structural determinant for the basic membrane interaction. The circular dichroism and nuclear magnetic resonance results revealed that in a membrane-mimetic environment, the active peptides adopt a more stabilized helical conformation than that of the inactive fragment, and this conformation conferred an overall amphipathicity to the active peptides. Therefore, the most decisive factor responsible for the activity and selectivity could be the intramolecular amphipathic cooperativity, rather than the amphipathicity itself. Especially, the tryptophan residue of the active peptides seems to play a crucial role at the critical amphipathic interface that promotes and balances the amphipathic cooperativity by stabilizing both the hydrophilic and hydrophobic interactions with the membrane. Altogether, the present results suggest that the two novel undecapeptides are worthy of therapeutic development as new antibiotic and anticancer agents and provide structural information about their action mechanism.
authors.affiliation: Department of Biotechnology, Division of Life Sciences, College of Biomedical & Health Science, Konkuk University, Chungju, Chungbuk 380-701, Korea.
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Won
authors.forename: Min-Duk
authors.initials: MD
authors.lastname: Seo
authors.forename: Seo-Jeong
authors.initials: SJ
authors.lastname: Jung
authors.forename: Sang-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kang
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Son
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tae-Kyu
authors.initials: TK
authors.lastname: Park
authors.forename: Sung-Jean
authors.initials: SJ
authors.lastname: Park
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D011498:Protein Precursors / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D009842:Oligopeptides; D010455:Peptides; D011498:Protein Precursors; C096397:gaegurin 5