Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures

Detalhes bibliográficos
Autor(a) principal: Ramos, Catarina I. V.
Data de Publicação: 2019
Outros Autores: Almeida, Susana P., Lourenço, Leandro M. O., Pereira, Patrícia M. R., Fernandes, Rosa, Faustino, M. Amparo F., Tomé, João P. C., Carvalho, Josué, Cruz, Carla, Neves, M. Graça P. M. S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/107169
https://doi.org/10.3390/molecules24040733
Resumo: The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.
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spelling Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structuresmulticharged phthalocyaninesG-Quadruplexestelomerase inhibitionselectivitysalmon sperm DNAUV-VishyperchromismG4-FIDcircular dichroismThe stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.MDPI2019-02-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107169http://hdl.handle.net/10316/107169https://doi.org/10.3390/molecules24040733eng1420-3049307816751420-3049Ramos, Catarina I. V.Almeida, Susana P.Lourenço, Leandro M. O.Pereira, Patrícia M. R.Fernandes, RosaFaustino, M. Amparo F.Tomé, João P. C.Carvalho, JosuéCruz, CarlaNeves, M. Graça P. M. S.info: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:RCAAP2023-06-13T08:36:20Zoai:estudogeral.uc.pt:10316/107169Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:31.776506Repositório 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 Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
title Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
spellingShingle Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
Ramos, Catarina I. V.
multicharged phthalocyanines
G-Quadruplexes
telomerase inhibition
selectivity
salmon sperm DNA
UV-Vis
hyperchromism
G4-FID
circular dichroism
title_short Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
title_full Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
title_fullStr Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
title_full_unstemmed Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
title_sort Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
author Ramos, Catarina I. V.
author_facet Ramos, Catarina I. V.
Almeida, Susana P.
Lourenço, Leandro M. O.
Pereira, Patrícia M. R.
Fernandes, Rosa
Faustino, M. Amparo F.
Tomé, João P. C.
Carvalho, Josué
Cruz, Carla
Neves, M. Graça P. M. S.
author_role author
author2 Almeida, Susana P.
Lourenço, Leandro M. O.
Pereira, Patrícia M. R.
Fernandes, Rosa
Faustino, M. Amparo F.
Tomé, João P. C.
Carvalho, Josué
Cruz, Carla
Neves, M. Graça P. M. S.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ramos, Catarina I. V.
Almeida, Susana P.
Lourenço, Leandro M. O.
Pereira, Patrícia M. R.
Fernandes, Rosa
Faustino, M. Amparo F.
Tomé, João P. C.
Carvalho, Josué
Cruz, Carla
Neves, M. Graça P. M. S.
dc.subject.por.fl_str_mv multicharged phthalocyanines
G-Quadruplexes
telomerase inhibition
selectivity
salmon sperm DNA
UV-Vis
hyperchromism
G4-FID
circular dichroism
topic multicharged phthalocyanines
G-Quadruplexes
telomerase inhibition
selectivity
salmon sperm DNA
UV-Vis
hyperchromism
G4-FID
circular dichroism
description The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.
publishDate 2019
dc.date.none.fl_str_mv 2019-02-18
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/10316/107169
http://hdl.handle.net/10316/107169
https://doi.org/10.3390/molecules24040733
url http://hdl.handle.net/10316/107169
https://doi.org/10.3390/molecules24040733
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1420-3049
30781675
1420-3049
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dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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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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