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http://hdl.handle.net/2445/178408
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DC Field | Value | Language |
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dc.contributor.author | Gallo, Maria | - |
dc.contributor.author | Moreno Guillén, 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, Leonardo | - |
dc.contributor.author | Maldonado, Rafael | - |
dc.contributor.author | Andreu, David | - |
dc.date.accessioned | 2021-06-16T13:18:37Z | - |
dc.date.available | 2022-04-22T05:10:24Z | - |
dc.date.issued | 2021-04-22 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/2445/178408 | - |
dc.description.abstract | The 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.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Chemical Society | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.1c00484 | - |
dc.relation.ispartof | Journal of Medicinal Chemistry, 2021, vol. 64, num. 10, p. 6937-6948 | - |
dc.relation.uri | https://doi.org/10.1021/acs.jmedchem.1c00484 | - |
dc.rights | (c) American Chemical Society , 2021 | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Cànnabis | - |
dc.subject.classification | Tractament del dolor | - |
dc.subject.classification | Pèptids | - |
dc.subject.other | Cannabis | - |
dc.subject.other | Pain treatment | - |
dc.subject.other | Peptides | - |
dc.title | Orally active peptide vector allows using cannabis to fight pain while avoiding side effects | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 711916 | - |
dc.date.updated | 2021-06-16T13:18:37Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
Files in This Item:
File | Description | Size | Format | |
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711916.pdf | 6.93 MB | Adobe PDF | View/Open |
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