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dc.contributor.authorGallo, Mariaa-
dc.contributor.authorMoreno Guillén, Estefanía-
dc.contributor.authorDefaus, Sira-
dc.contributor.authorOrtega-Alvaro, Antonio-
dc.contributor.authorGonzalez, Angel-
dc.contributor.authorRobledo, Patricia-
dc.contributor.authorCavaco, Marco-
dc.contributor.authorNeves, Vera-
dc.contributor.authorCastanho, Miguel A.R.B.-
dc.contributor.authorCasadó, Vicent-
dc.contributor.authorPardo, Leonardo-
dc.contributor.authorMaldonado, Rafael-
dc.contributor.authorAndreu, David-
dc.description.abstractThe activation of cannabinoid CB1 receptors (CB1R) by Δ9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, induces analgesia. CB1R activation, however, also causes cognitive impairment via the serotonin 5HT2A receptor (5HT2AR), a component of a CB1R−5HT2AR heteromer, posing a serious drawback for cannabinoid therapeutic use. We have shown that peptides reproducing CB1R transmembrane (TM) helices 5 and 6, fused to a cell-penetrating sequence (CPP), can alter the structure of the CB1R−5HT2AR heteromer and avert THC cognitive impairment while preserving analgesia. Here, we report the optimization of these prototypes into drug-like leads by (i) shortening the TM5, TM6, and CPP sequences, without losing the ability to disturb the CB1R−5HT2AR heteromer, and (ii) extensive sequence remodeling to achieve protease resistance and blood−brain barrier penetration. Our efforts have culminated in the identification of an ideal candidate for cannabis-based pain management, an orally active 16-residue peptide preserving THC-induced analgesia.-
dc.format.extent12 p.-
dc.publisherAmerican Chemical Society-
dc.relation.isformatofVersió postprint del document publicat a:
dc.relation.ispartofJournal of Medicinal Chemistry, 2021, vol. 64, num. 10, p. 6937-6948-
dc.rights(c) American Chemical Society , 2021-
dc.subject.classificationTractament del dolor-
dc.subject.otherPain treatment-
dc.titleOrally active peptide vector allows using cannabis to fight pain while avoiding side effects-
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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