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https://hdl.handle.net/10316/113883
Título: | Insights into the Degradation of Polymer-Drug Conjugates by an Overexpressed Enzyme in Cancer Cells | Autor: | Figueiredo, Pedro R. González, Ricardo D. Carvalho, Alexandra T. P. |
Data: | 23-Fev-2023 | Editora: | American Chemical Society | Projeto: | grant SFRH/BD/144303/ 2019 grant 2020.10114.BD grant IF/01272/2015 UIDB/04539/2020 |
Título da revista, periódico, livro ou evento: | Journal of Medicinal Chemistry | Volume: | 66 | Número: | 4 | Resumo: | Intensive efforts have been made to provide better treatments to cancer patients. Currently, nanoparticle-based drug delivery systems have gained propulsion, as they can overcome the drawbacks of free drugs. However, drug stability inside the nanocapsule must be ensured to prevent burst release. To overcome this, drugs conjugated to amphiphilic copolymers, assembled into nanoparticles, can provide a sustained release if endogenously degraded. Thus, we have designed and assessed the drug release viability of polymer-drug conjugates by the human Carboxylesterase 2, for a targeted drug activation. We performed molecular dynamics simulations applying a quantum mechanics/molecular mechanics potential to study the degradation profiles of 30 designed conjugates, where six were predicted to be hydrolyzed by this enzyme. We further analyzed the enzyme-substrate environment to delve into what structural features may lead to successful hydrolysis. These findings contribute to the development of new medicines ensuring effective cancer treatments with fewer side effects. | URI: | https://hdl.handle.net/10316/113883 | ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/acs.jmedchem.2c01781 | Direitos: | openAccess |
Aparece nas coleções: | IIIUC - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Insights-into-the-Degradation-of-PolymerDrug-Conjugates-by-an-Overexpressed-Enzyme-in-Cancer-CellsJournal-of-Medicinal-Chemistry.pdf | 9.87 MB | Adobe PDF | Ver/Abrir |
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