title: The wewakpeptins, cyclic depsipeptides from a Papua New Guinea collection of the marine cyanobacterium Lyngbya semiplena.
abstract: Four new depsipeptides have been isolated from the marine cyanobacterium Lyngbya semiplena collected from Papua New Guinea. The amino and hydroxy acid partial structures of wewakpeptins A-D (1-4) were elucidated through extensive spectroscopic techniques, including HR-FABMS, 1D (1)H and (13)C NMR, as well as 2D COSY, HSQC, HSQC-TOCSY, and HMBC spectra. The sequence of the residues was determined through a combination of multifaceted approaches including ESI-MS/MS, HMBC, ROESY, and a modified 1D HMBC experiment. The absolute stereochemistry of each residue was determined by chiral HPLC and chiral GC-MS methods. The wewakpeptins represent an unusual arrangement of amino and hydroxy acid subunits relative to known cyanobacterial peptides and possess a bis-ester, a 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya) or 2,2-dimethyl-3-hydroxyoctanoic acid (Dhoaa) residue, and a diprolyl group reminiscent of dolastatin 15. Wewakpeptin A and B were the most cytotoxic among these four depsipeptides with an LC(50) of approximately 0.4 muM to both the NCI-H460 human lung tumor and the neuro-2a mouse neuroblastoma cell lines.
authors.affiliation: College of Pharmacy and Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Bingnan
authors.initials: B
authors.lastname: Han
authors.forename: Doug
authors.initials: D
authors.lastname: Goeger
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Maier
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C500107:wewakpeptin A; C500108:wewakpeptin B