Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors

Detalhes bibliográficos
Autor(a) principal: Hollmann, Axel
Data de Publicação: 2014
Outros Autores: Castanho, Miguel A. R. B., Lee, Benhur, Santos, Nuno C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/23084
Resumo: © 2014 Biochemical Society ©The Authors Journal compilation
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spelling Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitorsAnisotropyFusion inhibitionGeneralized polarizationHIV-1Membrane fusionSinglet oxygen© 2014 Biochemical Society ©The Authors Journal compilationIt was reported recently that a new aryl methyldiene rhodamine derivative, LJ001, and oxazolidine-2,4-dithione, JL103, act on the viral membrane, inhibiting its fusion with a target cell membrane. The aim of the present study was to investigate the interactions of these two active compounds and an inactive analogue used as a negative control, LJ025, with biological membrane models, in order to clarify the mechanism of action at the molecular level of these new broad-spectrum enveloped virus entry inhibitors. Fluorescence spectroscopy was used to quantify the partition and determine the location of the molecules on membranes. The ability of the compounds to produce reactive oxygen molecules in the membrane was tested using 9,10-dimethylanthracene, which reacts selectively with singlet oxygen (1O2). Changes in the lipid packing and fluidity of membranes were assessed by fluorescence anisotropy and generalized polarization measurements. Finally, the ability to inhibit membrane fusion was evaluated using FRET. Our results indicate that 1O2 production by LJ001 and JL103 is able to induce several changes on membrane properties, specially related to a decrease in its fluidity, concomitant with an increase in the order of the polar headgroup region, resulting in an inhibition of the membrane fusion necessary for cell infection.This work was funded by Fundação para a Ciência e Tecnologia – Ministério da Educação e Ciência (FCT-MEC, Portugal) [projects PTDC/QUI-BIQ/104787/2008 and VIH/SAU/0047/2011]. A.H. also acknowledges a FCT-MEC fellowship [number SFRH/BPD/72037/2010]. B.L. was supported by the National Institutes of Health [grant numbers U01 AI070495 and U01 AI082100].Portland PressRepositório da Universidade de LisboaHollmann, AxelCastanho, Miguel A. R. B.Lee, BenhurSantos, Nuno C.2016-03-18T15:15:41Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/23084engBiochem. J. (2014) 459, 161–1700264-6021doi:10.1042/BJ20131058metadata only accessinfo: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:RCAAP2023-11-08T16:10:53Zoai:repositorio.ul.pt:10451/23084Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:40:33.582961Repositório 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 Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
title Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
spellingShingle Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
Hollmann, Axel
Anisotropy
Fusion inhibition
Generalized polarization
HIV-1
Membrane fusion
Singlet oxygen
title_short Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
title_full Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
title_fullStr Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
title_full_unstemmed Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
title_sort Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
author Hollmann, Axel
author_facet Hollmann, Axel
Castanho, Miguel A. R. B.
Lee, Benhur
Santos, Nuno C.
author_role author
author2 Castanho, Miguel A. R. B.
Lee, Benhur
Santos, Nuno C.
author2_role author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Hollmann, Axel
Castanho, Miguel A. R. B.
Lee, Benhur
Santos, Nuno C.
dc.subject.por.fl_str_mv Anisotropy
Fusion inhibition
Generalized polarization
HIV-1
Membrane fusion
Singlet oxygen
topic Anisotropy
Fusion inhibition
Generalized polarization
HIV-1
Membrane fusion
Singlet oxygen
description © 2014 Biochemical Society ©The Authors Journal compilation
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2016-03-18T15:15:41Z
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/10451/23084
url http://hdl.handle.net/10451/23084
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biochem. J. (2014) 459, 161–170
0264-6021
doi:10.1042/BJ20131058
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Portland Press
publisher.none.fl_str_mv Portland Press
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
instacron_str RCAAP
institution RCAAP
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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