Cell-penetrating peptides as drug shuttles for pain management and other therapeutic applications
This thesis focuses on one of the biggest challenges facing drug discovery field: the efficient targeted delivery of therapeutic compounds, and how cell-penetrating peptides (CPPs) acting as drug delivery vectors can overcome pharmacokinetic issues and poor access to difficult targets, such as the c...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/672621 |
| Acceso en línea: | http://hdl.handle.net/10803/672621 |
| Access Level: | acceso abierto |
| Palabra clave: | Cell-penetrating peptides G-protein coupled receptors Tetrahydrocannabinol (THC) CNS disorders Parasitic infections Péptidos de penetración cellular Receptores acoplados a proteínas Receptores acoplados a proteínas G Transtornos del SNC Infecciones parasitarias 615 |
| Sumario: | This thesis focuses on one of the biggest challenges facing drug discovery field: the efficient targeted delivery of therapeutic compounds, and how cell-penetrating peptides (CPPs) acting as drug delivery vectors can overcome pharmacokinetic issues and poor access to difficult targets, such as the central nervous system (CNS). Specifically, we designed and developed an optimized, oral active, CPP-linked peptide-based disruptor targeting cannabinoid CB1 and serotonin 5HT2A receptor heterodimer, which allows medical use of cannabinoids to fight pain while avoiding memory impairment side effects. Similarly, we successfully disturbed the adenosine A2A receptor homodimerization by coupling an interfering peptide to a modified cyclic CPP, as a promising strategy for treatment of CNS disorders. Following also CPP-conjugation, we managed to considerably increase cellular uptake into Leishmania cells of paromomycin, a low bioavailable anti-parasitic drug. Altogether, this work reinforces CPPs relevance as drug carriers and provides valuable insights into CPPs design, optimization, validation and coupling strategies. |
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