title: Identification by 19F NMR of traditional Chinese medicinal plants possessing prolyl oligopeptidase inhibitory activity.
abstract: Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes proline-containing peptides at the carboxy termini of the proline residues. This peptidase has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders and might therefore have important clinical implications. Traditional Chinese medicinal (TCM) plants provide a rich source of unexplored compounds for strategies to find novel POP inhibitors, but the traditional methodologies used to identify POP inhibitors could have some limitations when working with natural products: interference with the colorimetric or fluorimetric detection methods commonly used to screen for POP inhibitors can result in the generation of false positives or false negatives. Since NMR screening is less prone to such interference, we decided to explore the use of 19F NMR to screen for POP inhibitors. We synthesized a new 19F-labeled POP substrate--Z-Gly-Pro-Phe-4(CF3)-NH2--and used it to search for new POP inhibitors in TCM plant extracts. We identified several plants with high POP-inhibitory activity and show here that the combination of 19F NMR and TCM plant extracts is a useful tool for identifying new POP inhibitors.
authors.affiliation: Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Josep Samitier 1-5, 08028 Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tarragó
authors.forename: Silvia
authors.initials: S
authors.lastname: Frutos
authors.forename: Ricard A
authors.initials: RA
authors.lastname: Rodriguez-Mias
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D008516:Medicine, Chinese Traditional; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D012015:Reference Standards; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000187:drug effects; D013997:Time Factors
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D010455:Peptides; D005461:Fluorine; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases