PMID: 9432007Feb 7, 1998Paper

Development and evaluation of peptide-based prolyl oligopeptidase inhibitors--introduction of N-benzyloxycarbonyl-prolyl-3-fluoropyrrolidine as a lead in inhibitor design

European Journal of Biochemistry
F GoossensS Scharpé

Abstract

The current study has been undertaken to develop new and biocompatible inhibitors for prolyl oligopeptidase, a highly specific endopeptidase, proposed to be involved, through its affinity for neuropeptides and kinins, in the processes of learning and memory and in the control of blood pressure. For in vitro evaluation of the inhibitors, human platelet prolyl oligopeptidase was purified to homogeneity and characterized. Northern blot analysis showed that mRNA coding for prolyl oligopeptidase was present in all tissues examined and only one transcript of 3.1 kb was detected. In addition to the human platelet enzyme, we also purified rat brain prolyl oligopeptidase, which proved to have the same characteristics as the human enzyme. In a series of tested peptides, bradykinin was found to be the best substrate. Based on this information, peptides bearing pseudopeptide bonds were generated and evaluated as inhibitors. The experiments clearly demonstrated that changes to the scissile peptide bond significantly decrease the affinity of prolyl oligopeptidase for the peptide derivatives. In our series of synthetic N-terminal blocked dipeptides, N-benzyloxycarbonyl-prolyl-3-fluoropyrrolidine was the most potent compound. Inhibition was re...Continue Reading

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Citations

May 6, 2011·Journal of Molecular Histology·Shin MatsubaraAtsushi P Kimura
Nov 13, 2003·Bioorganic & Medicinal Chemistry Letters·Gunther BalAchiel Haemers
Feb 28, 2007·BMC Psychiatry·Firoza MamdaniGustavo Turecki
Jan 2, 2007·Neuropeptides·J A García-HorsmanJ I Venäläinen
Jul 12, 2017·The Journal of Organic Chemistry·Tsugio KitamuraAnd Juzo Oyamada
May 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jianlin HanTsugio Kitamura
Sep 20, 2012·Chemistry : a European Journal·Lorraine E CombettesVéronique Gouverneur

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