Probing the Anti-Sickling Power of Distinct Drugs in Sickle Cell Disease

Detalhes bibliográficos
Autor(a) principal: Neto, Vasco Miguel dos Santos
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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spelling 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
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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