Please use this identifier to cite or link to this item:
Title: Inhibition of human prolyl oligopeptidase activity by the Cyclotide Psysol 2 isolated from Psychotria solitudinum
Author: Hellinger, Roland
Koehbach, Johannes
Puigpinós, Albert
Clark, Richard J.
Tarragó Clua, Maria Teresa
Giralt Lledó, Ernest
Gruber, Christian W.
Keywords: Pèptids
Medicaments peptídics
Peptide drugs
Issue Date: 2015
Publisher: American Chemical Society
Abstract: Cyclotides are head-to-tail cyclized peptides comprising a stabilizing cystine-knot motif. To date, they are well known for their diverse bioactivities such as anti-HIV and immunosuppressive properties. Yet little is known about specific molecular mechanisms, in particular the interaction of cyclotides with cellular protein targets. Native and synthetic cyclotide-like peptides from Momordica plants are potent and selective inhibitors of different serine-type proteinases such as trypsin, chymotrypsin, matriptase, and tryptase-beta. This study describes the bioactivity-guided isolation of a cyclotide from Psychotria solitudinum as an inhibitor of another serine-type protease, namely, the human prolyl oligopeptidase (POP). Analysis of the inhibitory potency of Psychotria extracts and subsequent fractionation by liquid chromatography yielded the isolated peptide psysol 2 (1), which exhibited an IC50 of 25 μM. In addition the prototypical cyclotide kalata B1 inhibited POP activity with an IC50 of 5.6 μM. The inhibitory activity appeared to be selective for POP, since neither psysol 2 nor kalata B1 were able to inhibit the proteolytic activity of trypsin or chymotrypsin. The enzyme POP is well known for its role in memory and learning processes, and it is currently being considered as a promising therapeutic target for the cognitive deficits associated with several psychiatric and neurodegenerative diseases, such as schizophrenia and Parkinson's disease. In the context of discovery and development of POP inhibitors with beneficial ADME properties, cyclotides may be suitable starting points considering their stability in biological fluids and possible oral bioavailability.
Note: Versió postprint del document publicat a:
It is part of: Journal of Natural Products, 2015, vol. 78, num. 5, p. 1073-1082
Related resource:
ISSN: 0163-3864
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

Files in This Item:
File Description SizeFormat 
652558.pdf3.25 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons