Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides

Novel strategies in the design of HIV-I fusion/entry inhibitors are based on the construction of dual- targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual -targeting peptides composed of peptide domains of E2 and El envelope proteins...

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Autores: Gómara Elena, María José, Pérez, Yolanda|||0000-0003-3767-5346, Martinez, Javier P.|||0000-0003-3333-5272, Barnadas Rodríguez, Ramon|||0000-0002-5775-6998, Schultz, Anke, von Briesen, Hagen, Peralvarez-Marin, Alex|||0000-0002-3457-0875, Meyerhans, Andreas|||0000-0003-0620-5317, Haro, Isabel|||0000-0001-8677-2340
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:205800
Acceso en línea:https://ddd.uab.cat/record/205800
https://dx.doi.org/urn:doi:10.1038/s41598-019-40125-4
Access Level:acceso abierto
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spelling Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor PeptidesGómara Elena, María JoséPérez, Yolanda|||0000-0003-3767-5346Martinez, Javier P.|||0000-0003-3333-5272Barnadas Rodríguez, Ramon|||0000-0002-5775-6998Schultz, Ankevon Briesen, HagenPeralvarez-Marin, Alex|||0000-0002-3457-0875Meyerhans, Andreas|||0000-0003-0620-5317Haro, Isabel|||0000-0001-8677-2340Novel strategies in the design of HIV-I fusion/entry inhibitors are based on the construction of dual- targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual -targeting peptides composed of peptide domains of E2 and El envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-I gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein(domain 139-156) which interacts with the HIV-I fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target. 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/205800https://dx.doi.org/urn:doi:10.1038/s41598-019-40125-4reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2058002026-06-06T12:50:31Z
dc.title.none.fl_str_mv Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
title Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
spellingShingle Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
Gómara Elena, María José
title_short Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
title_full Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
title_fullStr Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
title_full_unstemmed Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
title_sort Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
dc.creator.none.fl_str_mv Gómara Elena, María José
Pérez, Yolanda|||0000-0003-3767-5346
Martinez, Javier P.|||0000-0003-3333-5272
Barnadas Rodríguez, Ramon|||0000-0002-5775-6998
Schultz, Anke
von Briesen, Hagen
Peralvarez-Marin, Alex|||0000-0002-3457-0875
Meyerhans, Andreas|||0000-0003-0620-5317
Haro, Isabel|||0000-0001-8677-2340
author Gómara Elena, María José
author_facet Gómara Elena, María José
Pérez, Yolanda|||0000-0003-3767-5346
Martinez, Javier P.|||0000-0003-3333-5272
Barnadas Rodríguez, Ramon|||0000-0002-5775-6998
Schultz, Anke
von Briesen, Hagen
Peralvarez-Marin, Alex|||0000-0002-3457-0875
Meyerhans, Andreas|||0000-0003-0620-5317
Haro, Isabel|||0000-0001-8677-2340
author_role author
author2 Pérez, Yolanda|||0000-0003-3767-5346
Martinez, Javier P.|||0000-0003-3333-5272
Barnadas Rodríguez, Ramon|||0000-0002-5775-6998
Schultz, Anke
von Briesen, Hagen
Peralvarez-Marin, Alex|||0000-0002-3457-0875
Meyerhans, Andreas|||0000-0003-0620-5317
Haro, Isabel|||0000-0001-8677-2340
author2_role author
author
author
author
author
author
author
author
description Novel strategies in the design of HIV-I fusion/entry inhibitors are based on the construction of dual- targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual -targeting peptides composed of peptide domains of E2 and El envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-I gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein(domain 139-156) which interacts with the HIV-I fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target.
publishDate 2019
dc.date.none.fl_str_mv 2
2019-01-01
2019
2019-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/205800
https://dx.doi.org/urn:doi:10.1038/s41598-019-40125-4
url https://ddd.uab.cat/record/205800
https://dx.doi.org/urn:doi:10.1038/s41598-019-40125-4
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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