Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Gomara, Maria J.
• dc.contributor.author Pérez, Yolanda
• dc.contributor.author Gómez Gutiérrez, Patrícia
• dc.contributor.author Herrera, Carolina
• dc.contributor.author Ziprin, Paul
• dc.contributor.author Martínez, Javier P.
• dc.contributor.author Meyerhans, Andreas
• dc.contributor.author Pérez, Juan J.
• dc.contributor.author Haro, Isabel
• dc.date.accessioned 2020-10-08T06:16:01Z
• dc.date.available 2020-10-08T06:16:01Z
• dc.date.issued 2020
• dc.description.abstract Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations. Both parent and retro-enantio peptides demonstrate a topology compatible with a shared helix-turn-helix conformation and assemble similarly in the membrane maintaining the active conformation needed for its interaction with the viral target site. This study represents a straightforward approach to design new targeted peptides as HIV-1 fusion inhibitors and lead us to define a retro-enantio peptide as a good candidate for pre-exposure prophylaxis against HIV-1.
• dc.description.sponsorship Financial support from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and the European Regional Development Fund (Grant RTI2018-094120-B-I00 to I.H.) is gratefully acknowledged. A.M. is supported by a grant SAF2016-75505-R (AEI/MINECO/FEDER, UE) and through the “María de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0370). The 500-MHz spectrometer was purchased in part through a Research Infraestructure MINECO-FEDER fund (Grant CSIC13-4E-2076). Partial financial support from the Spanish National Research Council (CSIC) is also gratefully acknowledged.
• dc.format.mimetype application/pdf
• dc.identifier.citation Gomara MJ, Perez Y, Gomez-Gutierrez P, Herrera C, Ziprin P, Martinez JP, Meyerhans A, Perez JJ, Haro I. Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide. Sci Rep. 2020; 10(1):14430. DOI: 10.1038/s41598-020-71404-0
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-020-71404-0
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/45423
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Sci Rep. 2020; 10(1):14430
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75505-R
• dc.rights © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Biophysics
• dc.subject.keyword Chemical biology
• dc.subject.keyword Diseases
• dc.title Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion