2026-04-17T06:47:25Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1585842025-11-19T20:56:00Zcom_2072_1057col_2072_478917col_2072_478933
RECERCAT author Hellinger, Roland author Koehbach, Johannes author Puigpinós, Albert author Clark, Richard J. author Tarragó Clua, Maria Teresa author Giralt Lledó, Ernest author Gruber, Christian W. 2020-05-04T15:14:21Z2020-05-04T15:14:21Z20152020-05-04T15:14:21Z 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. cc-by (c) Hellinger, Rolland et al., 2015 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Pèptids Medicaments peptídics Peptides Peptide drugs Inhibition of human prolyl oligopeptidase activity by the Cyclotide Psysol 2 isolated from Psychotria solitudinum info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion