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 | Bingnan Han, Doug Goeger, Claudia S Maier, William H Gerwick |
Journal | The Journal of organic chemistry
(J Org Chem)
Vol. 70
Issue 8
Pg. 3133-9
(Apr 15 2005)
ISSN: 0022-3263 [Print] United States |
PMID | 15822975
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antineoplastic Agents
- Depsipeptides
- wewakpeptin A
- wewakpeptin B
|
Topics |
- Amino Acid Sequence
- Animals
- Antineoplastic Agents
(chemistry, isolation & purification, pharmacology)
- Cyanobacteria
(chemistry)
- Depsipeptides
(chemistry, isolation & purification, pharmacology)
- Drug Screening Assays, Antitumor
- Humans
- Mice
- Molecular Structure
- Nuclear Magnetic Resonance, Biomolecular
- Papua New Guinea
- Tumor Cells, Cultured
|