Web of Science: 10 cites, Scopus: 10 cites, Google Scholar: cites,
Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides
Gómara Elena, María José (Institut de Química Avançada de Catalunya)
Pérez, Yolanda (Institut de Química Avançada de Catalunya)
Martinez, Javier P. (Universitat Pompeu Fabra)
Barnadas Rodríguez, Ramon (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Schultz, Anke (Fraunhofer Institute for Biomedical Engineering (Sulzbach, Alemanya))
von Briesen, Hagen (Fraunhofer Institute for Biomedical Engineering (Sulzbach, Alemanya))
Peralvarez-Marin, Alex (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Meyerhans, Andreas (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Haro, Isabel (Institut de Química Avançada de Catalunya)

Data: 2019
Resum: 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.
Drets: Aquest 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. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Publicat a: Scientific reports, Vol. 9 (2019) , art. 3257, ISSN 2045-2322

DOI: 10.1038/s41598-019-40125-4
PMID: 30824796


13 p, 2.1 MB

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 Registre creat el 2019-06-17, darrera modificació el 2023-07-11



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