Publication
Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors
| dc.contributor.author | Hollmann, Axel | |
| dc.contributor.author | Castanho, Miguel A. R. B. | |
| dc.contributor.author | Lee, Benhur | |
| dc.contributor.author | Santos, Nuno C. | |
| dc.date.accessioned | 2016-03-18T15:15:41Z | |
| dc.date.available | 2016-03-18T15:15:41Z | |
| dc.date.issued | 2014 | |
| dc.description | © 2014 Biochemical Society ©The Authors Journal compilation | pt_PT |
| dc.description.abstract | It 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. | pt_PT |
| dc.description.sponsorship | 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]. | pt_PT |
| dc.identifier.citation | Biochem. J. (2014) 459, 161–170 | pt_PT |
| dc.identifier.doi | doi:10.1042/BJ20131058 | pt_PT |
| dc.identifier.issn | 0264-6021 | |
| dc.identifier.uri | http://hdl.handle.net/10451/23084 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Portland Press | pt_PT |
| dc.relation | Cell membrane features in HIV entry and its inhibition | |
| dc.relation | Multi-target HIV entry inhibitors delivery by cationic liposomes | |
| dc.relation.publisherversion | http://www.biochemj.org/ | pt_PT |
| dc.subject | Anisotropy | pt_PT |
| dc.subject | Fusion inhibition | pt_PT |
| dc.subject | Generalized polarization | pt_PT |
| dc.subject | HIV-1 | pt_PT |
| dc.subject | Membrane fusion | pt_PT |
| dc.subject | Singlet oxygen | pt_PT |
| dc.title | Singlet oxygen effects on lipid membranes : implications for the mechanism of action of broad-spectrum viral fusion inhibitors | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Cell membrane features in HIV entry and its inhibition | |
| oaire.awardTitle | Multi-target HIV entry inhibitors delivery by cationic liposomes | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-BIQ%2F104787%2F2008/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/VIH%2FSAU%2F0047%2F2011/PT | |
| oaire.citation.endPage | 170 | pt_PT |
| oaire.citation.title | Biochemical Journal | pt_PT |
| oaire.fundingStream | 3599-PPCDT | |
| oaire.fundingStream | 3599-PPCDT | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | closedAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isProjectOfPublication | aea345fc-1827-44ac-911d-545a3bd497a3 | |
| relation.isProjectOfPublication | c2649ab8-aa18-47dc-a765-4a1f94c70549 | |
| relation.isProjectOfPublication.latestForDiscovery | c2649ab8-aa18-47dc-a765-4a1f94c70549 |