Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/63293 |
Resumo: | Tese de mestrado, Bioquímica e Biomedicina, 2023, Universidade de Lisboa, Faculdade de Ciências |
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Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell DiseaseAnemia FalciformeSangueHemoglobinaDocking MolecularDinâmica MolecularTeses de mestrado - 2023Departamento de Química e BioquímicaTese de mestrado, Bioquímica e Biomedicina, 2023, Universidade de Lisboa, Faculdade de CiênciasSickle cell disease (SCD) is a genetic blood disorder that affects millions of people worldwide. The disease is characterized by anemia, pain crises, and a higher risk of stroke and heart attack. SCD is caused by a mutation in the gene that encodes the β subunit of hemoglobin, originating an abnormal form of hemoglobin known as HbS, where a Glu-β6 is replaced by a Val-β6 in the β-globins. The aggregation of this protein is responsible for the disease and is therefore a worthwhile target for drug activity. Despite being investigated for years, an easily applicable, reliable, and cheap treatment remains elusive. Therefore, it is essential to search for novel inhibitors for treatment of this illness. The focus of this thesis is identification and investigation of the potential therapeutic effect of several molecules identified through in silico methodologies to probe their specificity and anti-sickling potential via blockage of the pocket involved in the formation of fibers or other areas of the protein surface. For this purpose, molecular docking was initially used to screen a commercially available compound database as well as a number of drugs previously identified through in vitro studies. The screening focused on the hydrophobic pocket where the mutated Val residue is lodged in the fibers. Three high scoring and three low-scoring compounds from molecular docking were selected for further studies. Docking did not reveal a significant difference between these two sets, with both compound types featuring reported in vitro anti-sickling activity, exhibiting long pocket residence times and similar binding energies. All were found to bind with good affinity to the valine 6 residue, as observed in contact analysis through MD simulations. Future studies should consider other screening methodologies as well as additional simulations and in vitro experiments to assess the aggregation inhibition potential of these and related molecules.Galamba, Nuno Jorge Rosa Lopes, 1974-Victor, Bruno Lourenço da SilvaRepositório da Universidade de LisboaNeto, Vasco Miguel dos Santos202320232024-12-29T00:00:00Z2023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/63293enginfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T01:20:25Zoai:repositorio.ul.pt:10451/63293Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:14:32.230397Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
title |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
spellingShingle |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease Neto, Vasco Miguel dos Santos Anemia Falciforme Sangue Hemoglobina Docking Molecular Dinâmica Molecular Teses de mestrado - 2023 Departamento de Química e Bioquímica |
title_short |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
title_full |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
title_fullStr |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
title_full_unstemmed |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
title_sort |
Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease |
author |
Neto, Vasco Miguel dos Santos |
author_facet |
Neto, Vasco Miguel dos Santos |
author_role |
author |
dc.contributor.none.fl_str_mv |
Galamba, Nuno Jorge Rosa Lopes, 1974- Victor, Bruno Lourenço da Silva Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Neto, Vasco Miguel dos Santos |
dc.subject.por.fl_str_mv |
Anemia Falciforme Sangue Hemoglobina Docking Molecular Dinâmica Molecular Teses de mestrado - 2023 Departamento de Química e Bioquímica |
topic |
Anemia Falciforme Sangue Hemoglobina Docking Molecular Dinâmica Molecular Teses de mestrado - 2023 Departamento de Química e Bioquímica |
description |
Tese de mestrado, Bioquímica e Biomedicina, 2023, Universidade de Lisboa, Faculdade de Ciências |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023 2023 2023-01-01T00:00:00Z 2024-12-29T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/63293 |
url |
http://hdl.handle.net/10451/63293 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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