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 [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.
Witherup
K M
KM
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
Bogusky
M J
MJ
Anderson
P S
PS
Ramjit
H
H
Ransom
R W
RW
Wood
T
T
Sardana
M
M
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
D047169:Cyclotides; D010456:Peptides, Cyclic; C093020:cyclopsychotride A; D009496:Neurotensin; D002118:Calcium