title: 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.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Kwan
authors.forename: James R
authors.initials: JR
authors.lastname: Rocca
authors.forename: Khalil A
authors.initials: KA
authors.lastname: Abboud
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Paul
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luesch
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005431:Florida; D006801:Humans; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C528460:grassypeptolide