Internalization of methotrexate conjugates by folate receptor-α
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/57418 |
Resumo: | The folate antagonist methotrexate is a cytotoxic drug used in the treatment of several cancer types. Methotrexate entry into the cell is mediated by two main transport systems: the reduced folate carrier and membrane-associated folate receptors. These transporters differ considerably in their mechanism of (anti)folate uptake, substrate specificity and tissue specificity. Although the mechanism of action of the reduced folate carrier is fairly well-established, that of the folate receptor has remained doubtful. The development of specific folate receptor-targeted antifolates would be accelerated if additional mechanistic data becomes available. In this work, we used two fluorescent-labeled conjugates of methotrexate, differently linked at the terminal groups, to clarify the uptake mechanism by the folate receptor-α. The results demonstrate the importance of methotrexate amino groups in the interaction with the folate receptor-α. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Internalization of methotrexate conjugates by folate receptor-αScience & TechnologyThe folate antagonist methotrexate is a cytotoxic drug used in the treatment of several cancer types. Methotrexate entry into the cell is mediated by two main transport systems: the reduced folate carrier and membrane-associated folate receptors. These transporters differ considerably in their mechanism of (anti)folate uptake, substrate specificity and tissue specificity. Although the mechanism of action of the reduced folate carrier is fairly well-established, that of the folate receptor has remained doubtful. The development of specific folate receptor-targeted antifolates would be accelerated if additional mechanistic data becomes available. In this work, we used two fluorescent-labeled conjugates of methotrexate, differently linked at the terminal groups, to clarify the uptake mechanism by the folate receptor-α. The results demonstrate the importance of methotrexate amino groups in the interaction with the folate receptor-α.E.A. (SFRH/BD/122952/2016) and J.N. (SFRH/BD/121673/ 2016) hold scholarships from the Portuguese Foundation for Science and Technology (FCT). This study was supported by the FCT under the scope of the strategic funding of the UID/ BIO/04469/2013 unit and the COMPETE 2020 (POCI-010145-FEDER-006684) and BioTecNorte operation (NORTE01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020Programa Operacional Regional do Norte. This work has also received funding from the European Union 7th Framework Programme (FP7/2007−2013), under Grant Agreement NMP4-LA-2009228827 NANOFOL, and the Horizon 2020 research and innovation program under Grant Agreement NMP-06-2015683356 FOLSMART.info:eu-repo/semantics/publishedVersionAmerican Chemical SocietyUniversidade do MinhoNogueira, E.Passos, M.Azóia, Nuno G.Antunes, EgiptoLoureiro, AnaGuimarães, Diana Isabel PereiraJennifer NoroRollett, AlexandraGuebitz, Georg M.Cavaco-Paulo, Artur2018-11-192018-11-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/57418engNogueira, E.; Passos, M.; Azoia, Nuno G.; Antunes, Egipto; Loureiro, Ana; Guimarães, Diana Isabel Pereira; Jennifer Noro; Rollett, Alexandra; Guebitz, Georg M.; Cavaco-Paulo, Artur, Internalization of methotrexate conjugates by folate receptor-α. Biochemistry, 57(49), 6780-6786, 20180006-29601520-499510.1021/acs.biochem.8b0060730452231https://pubs.acs.org/journal/bichawinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:14:50Zoai:repositorium.sdum.uminho.pt:1822/57418Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:07:10.756908Repositório 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 |
Internalization of methotrexate conjugates by folate receptor-α |
title |
Internalization of methotrexate conjugates by folate receptor-α |
spellingShingle |
Internalization of methotrexate conjugates by folate receptor-α Nogueira, E. Science & Technology |
title_short |
Internalization of methotrexate conjugates by folate receptor-α |
title_full |
Internalization of methotrexate conjugates by folate receptor-α |
title_fullStr |
Internalization of methotrexate conjugates by folate receptor-α |
title_full_unstemmed |
Internalization of methotrexate conjugates by folate receptor-α |
title_sort |
Internalization of methotrexate conjugates by folate receptor-α |
author |
Nogueira, E. |
author_facet |
Nogueira, E. Passos, M. Azóia, Nuno G. Antunes, Egipto Loureiro, Ana Guimarães, Diana Isabel Pereira Jennifer Noro Rollett, Alexandra Guebitz, Georg M. Cavaco-Paulo, Artur |
author_role |
author |
author2 |
Passos, M. Azóia, Nuno G. Antunes, Egipto Loureiro, Ana Guimarães, Diana Isabel Pereira Jennifer Noro Rollett, Alexandra Guebitz, Georg M. Cavaco-Paulo, Artur |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Nogueira, E. Passos, M. Azóia, Nuno G. Antunes, Egipto Loureiro, Ana Guimarães, Diana Isabel Pereira Jennifer Noro Rollett, Alexandra Guebitz, Georg M. Cavaco-Paulo, Artur |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
The folate antagonist methotrexate is a cytotoxic drug used in the treatment of several cancer types. Methotrexate entry into the cell is mediated by two main transport systems: the reduced folate carrier and membrane-associated folate receptors. These transporters differ considerably in their mechanism of (anti)folate uptake, substrate specificity and tissue specificity. Although the mechanism of action of the reduced folate carrier is fairly well-established, that of the folate receptor has remained doubtful. The development of specific folate receptor-targeted antifolates would be accelerated if additional mechanistic data becomes available. In this work, we used two fluorescent-labeled conjugates of methotrexate, differently linked at the terminal groups, to clarify the uptake mechanism by the folate receptor-α. The results demonstrate the importance of methotrexate amino groups in the interaction with the folate receptor-α. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-11-19 2018-11-19T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/57418 |
url |
http://hdl.handle.net/1822/57418 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nogueira, E.; Passos, M.; Azoia, Nuno G.; Antunes, Egipto; Loureiro, Ana; Guimarães, Diana Isabel Pereira; Jennifer Noro; Rollett, Alexandra; Guebitz, Georg M.; Cavaco-Paulo, Artur, Internalization of methotrexate conjugates by folate receptor-α. Biochemistry, 57(49), 6780-6786, 2018 0006-2960 1520-4995 10.1021/acs.biochem.8b00607 30452231 https://pubs.acs.org/journal/bichaw |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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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 |
reponame_str |
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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1799132489961177088 |