title: Koshikamide B, a cytotoxic peptide lactone from a marine sponge Theonella sp.
abstract: Koshikamide B (1) has been isolated from two separate collections of the marine sponge Theonella sp. as the major cytotoxic constituent. Koshikamide B is a 17-residue peptide lactone composed of six proteinogenic amino acids, two D-isomers of proteinogenic amino acids, seven N-methylated amino acids, and two unusual amino acid residues. The unusual amino acids are N(delta)-carbamoylasparagine and 2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid (AHPP); the former is first found as the constituent of peptides, whereas the latter is a new amino acid residue. The N-terminus of koshikamide B is blocked by a methoxyacetyl group. The structure of koshikamide B (1) has been determined by interpretation of spectral data and analysis of chemical degradation products. Koshikamide B (1) exhibits cytotoxicity against P388 murine leukemia cells and the human colon tumor (HCT-116) cell line with an IC50 value of 0.45 and 7.5 microg/mL, respectively.
authors.affiliation: Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Araki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsunaga
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakao
authors.forename: Kazuo
authors.initials: K
authors.lastname: Furihata
authors.forename: Lyndon
authors.initials: L
authors.lastname: West
authors.forename: D John
authors.initials: DJ
authors.lastname: Faulkner
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fusetani
mesh_terms: D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000633:toxicity*; D011422:Propionates / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D047232:Theonella / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C534355:2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid; D007783:Lactones; C534354:N(delta)-carbamoylasparagine; D009842:Oligopeptides; D011422:Propionates; D011759:Pyrrolidines; C534353:koshikamide B; D001216:Asparagine