Total structure determination of grassypeptolide, a new marine cyanobacterial cytotoxin.

Abstract

A collection of the cyanobacterium Lyngbya confervoides off Grassy Key in Florida yielded grassypeptolide (1), a 31-membered macrocyclic depsipeptide with unusually high D-amino acid content, two thiazolines, and one beta-amino acid. We report the rigorous 3D structure determination and conformational analysis in solution and solid state by NMR, MS, X-ray crystallography, chemical degradation, and molecular modeling involving distance geometry and restrained molecular dynamics. Grassypeptolide (1) inhibited cancer cell growth with IC50 values from 1.0 to 4.2 microM.

• Authors: Jason C Kwan, James R Rocca, Khalil A Abboud, Valerie J Paul, Hendrik Luesch
• Journal: Organic letters (Org Lett) Vol. 10 Issue 5 Pg. 789-92 (Mar 06 2008) ISSN: 1523-7060 [Print] United States
• PMID: 18220404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Depsipeptides
• grassypeptolide

Topics

• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Crystallography, X-Ray
• Cyanobacteria (chemistry)
• Depsipeptides (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Florida
• Humans
• Inhibitory Concentration 50
• Marine Biology
• Molecular Conformation
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular