dc.contributor.author |
Gallo, Maria |
dc.contributor.author |
Moreno, Estefanía |
dc.contributor.author |
Defaus, Sira |
dc.contributor.author |
Ortega-Alvaro, Antonio |
dc.contributor.author |
Gonzalez, Angel |
dc.contributor.author |
Robledo, Patricia |
dc.contributor.author |
Cavaco, Marco |
dc.contributor.author |
Neves, Vera |
dc.contributor.author |
Castanho, Miguel A. R. B. |
dc.contributor.author |
Casadó, Vicent |
dc.contributor.author |
Pardo Carrasco, Leonardo |
dc.contributor.author |
Maldonado, Rafael |
dc.contributor.author |
Andreu Martínez, David |
dc.date |
2021 |
dc.identifier |
https://ddd.uab.cat/record/250419 |
dc.identifier |
urn:10.1021/acs.jmedchem.1c00484 |
dc.identifier |
urn:oai:ddd.uab.cat:250419 |
dc.identifier |
urn:pmcid:PMC8486167 |
dc.identifier |
urn:pmc-uid:8486167 |
dc.identifier |
urn:pmid:33887904 |
dc.identifier |
urn:articleid:15204804v64n10p6937 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:8486167 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/6b7ee91a-cdcf-4ee2-8964-b830e1f2842e |
dc.identifier |
urn:scopus_id:85106530090 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Agencia Estatal de Investigación SAF2017-87629-R |
dc.relation |
Agencia Estatal de Investigación PID2019-109240RB-I00 |
dc.relation |
Journal of Medicinal Chemistry ; Vol. 64 Núm. 10 (april 2021), p. 6937-6948 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.title |
Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects |
dc.type |
Article |
dc.description.abstract |
Altres ajuts: Rhodes Pharmaceuticals (L.P., Coventry, R.I., USA; 2016−2017), Marie Skłodowska-Curie Research and Innovation StaffExchange (call H2020-MSCA-RISE-2014, 2015−2019), and the Fundació Bancaria La Caixa (CaixaImpulse 2018 call; 2018-2020). |
dc.description.abstract |
The activation of cannabinoid CB receptors (CBR) by Δ 9 -tetrahydrocannabinol (THC), the main component of Cannabis sativa, induces analgesia. CBR activation, however, also causes cognitive impairment via the serotonin 5HT receptor (5HTR), a component of a CBR-5HTR heteromer, posing a serious drawback for cannabinoid therapeutic use. We have shown that peptides reproducing CBR transmembrane (TM) helices 5 and 6, fused to a cell-penetrating sequence (CPP), can alter the structure of the CBR-5HTR 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 CBR-5HTR 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. |