CYCLOPSYCHOTRIDE-A, A BIOLOGICALLY-ACTIVE, 31-RESIDUE CYCLIC PEPTIDE ISOLATED FROM PSYCHOTRIA-LONGIPES

A preliminary characterization is provided of a naturally occurring cyclic peptide with interesting and potent biological activity. A 31-residue cyclic peptide, designated cyclopsychotride A [1], was obtained from the organic extract of the tropical plant, Psychotria longipes. Compound 1 inhibited [I-125] neurotensin (NT) binding to HT-29 cell membranes (IC50 3 mu M) and also stimulated increased levels of cytosolic Ca2+ in two unrelated cell lines that do not express NT receptors. The peptide was found to dose-dependently increase intracellular Ca2+ at concentrations ranging from 3 to 30 mu M, and this response was not blocked by a known NT antagonist. Cyclopsychotride A [1] possesses three disulfide linkages and is thought to be the largest cyclic peptide isolated from a natural source. Both H-1-nmr and cd spectroscopy showed 1 to be highly structured.