title: Selective modification of the N-terminal structure of polytheonamide B significantly changes its cytotoxicity and activity as an ion channel.
abstract: Chemical point mutation: Polytheonamide B is a naturally occurring polypeptide containing 48 amino acids. It both displays potent cytotoxicity and acts as a monovalent cation channel in vitro. Chemoselective methods to modify the 44th, N-, and C-terminal residues of the natural product have been developed, and evaluation of the resultant derivatives suggests that the intrinsic activities of the peptide can only be altered by switching its N-terminal substitution.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shinohara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000633:toxicity; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D011506:Proteins; C111717:polytheonamide B; D012451:Safrole; C005746:sulfoxide