title: Cyclopsychotride A, a biologically active, 31-residue cyclic peptide isolated from Psychotria longipes.
abstract: 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 [125I] neurotensin (NT) binding to HT-29 cell membranes (IC50 3 microM) 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 microM, 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 1H-nmr and cd spectroscopy showed 1 to be highly structured.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: K M
authors.initials: KM
authors.lastname: Witherup
authors.forename: M J
authors.initials: MJ
authors.lastname: Bogusky
authors.forename: P S
authors.initials: PS
authors.lastname: Anderson
authors.forename: H
authors.initials: H
authors.lastname: Ramjit
authors.forename: R W
authors.initials: RW
authors.lastname: Ransom
authors.forename: T
authors.initials: T
authors.lastname: Wood
authors.forename: M
authors.initials: M
authors.lastname: Sardana
mesh_terms: D000595:Amino Acid Sequence; D001938:Brazil; D002118:Calcium / Q000378:metabolism; D002942:Circular Dichroism; D047169:Cyclotides; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000302:isolation & purification* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011487:Protein Conformation; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
chemical_list: D047169:Cyclotides; D010456:Peptides, Cyclic; C093020:cyclopsychotride A; D009496:Neurotensin; D002118:Calcium