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Functional Cell-Based Screening and Saturation Transfer Double-Difference NMR Have Identified Haplosamate A as a Cannabinoid Receptor Agonist

TitleFunctional Cell-Based Screening and Saturation Transfer Double-Difference NMR Have Identified Haplosamate A as a Cannabinoid Receptor Agonist
Publication TypeJournal Article
Year of Publication2009
AuthorsPereira, A, Pfeifer, TA, Grigliatti, TA, Andersen, RJ
JournalAcs Chemical Biology
Volume4
Pagination139-144
Date PublishedFeb
Type of ArticleArticle
ISBN Number1554-8929
KeywordsDOCKING, ENDOCANNABINOID SYSTEM, inhibitors, INTEGRIN ALPHA(IIB)BETA(3), LIGAND-BINDING, PEPTIDE, PROTEIN, SPECTROSCOPY, STD-NMR
Abstract

A marine natural product extract library has been screened with a functional cell-based G-protein coupled receptor assay to find compounds capable of binding the human cannabinoid receptors CB1 and CB2. The methanol extract of the marine sponge Dasychalina fragilis collected in Papua New Guinea was active in the assay. Bioassay guided fractionation of the extract identified the phosphorylated sterol sulfate haplosamate A(1) as a cannabinoid receptor agonist. The high water solubility of haplosamate A(1) allowed exploration of its binding interactions with the human cannabinoid recepors in whole insect cells by means of saturation transfer double-difference NMR spectroscopy. This technique confirmed that haplosamate A(1) binds selectively to these receptors.

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