| Autor | Bastian, Arangassery Rosemary | |
| Autor | Nangarlia, Aakansha | |
| Autor | Bailey, Lauren D | |
| Autor | Holmes, Andrew | |
| Autor | Sundaram, R. Venkat Kalyana | |
| Autor | Ang, Charles | |
| Autor | Moreira, Diogo Rodrigo Magalhães | |
| Autor | Freedman, Kevin | |
| Autor | Duffy, Caitlin | |
| Autor | Contarino, Mark | |
| Autor | Abrams, Cameron | |
| Autor | Root, Michael | |
| Autor | Chaiken, Irwin | |
| Data de acesso | 2015-06-01T19:02:22Z | |
| Data de disponibilização | 2016-01-01T06:30:04Z | |
| Data do publicação | 2015 | |
| Citação | BASTIAN, A. R. et al. Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation. Journal of Biological Chemistry, v. 290, n. 1, p. 529-543, 2015. | pt_BR |
| ISSN | 1083-351X | |
| URI | https://www.arca.fiocruz.br/handle/icict/10591 | |
| Idioma | por | pt_BR |
| Editor | American Society for Biochemistry and Molecular Biology | pt_BR |
| Direito Autoral | open access | pt_BR |
| Título | Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation. | pt_BR |
| Tipo do documento | Article | pt_BR |
| DOI | 10.1074/jbc.M114.608315 | |
| Resumo em Inglês | Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania / Drexel University. School of Biomedical Engineering. Science and Health Systems. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania / Drexel University. School of Biomedical Engineering. Science and Health Systems. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania / Drexel University. School of Biomedical Engineering. Science and Health Systems. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania / Drexel University. School of Biomedical Engineering. Science and Health Systems. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Afiliação | Drexel University. Department of Chemical and Biological Engineering. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University. Department of Chemical and Biological Engineering. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Jefferson University. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania | pt_BR |
| Afiliação | Drexel University College of Medicine. Department of Biochemistry and Molecular Biology. Philadelphia, Pennsylvania | pt_BR |
| DeCS | Fármacos Anti-HIV/farmacologia | pt_BR |
| DeCS | Proteína gp120 do Envelope de HIV/antagonistas & inibidores | pt_BR |
| DeCS | HIV-1/efeitos de drogas | pt_BR |
| DeCS | Nanoconjugados/toxicidade | pt_BR |
| DeCS | Peptídeos/farmacologia | pt_BR |
| DeCS | Triazóis/farmacologia | pt_BR |
| DeCS | Fármacos Anti-HIV/síntese química | pt_BR |
| DeCS | Linhagem Celular Tumoral | pt_BR |
| DeCS | Relação Dose-Resposta a Droga | pt_BR |
| DeCS | Ouro/química | pt_BR |
| DeCS | Proteína gp120 do Envelope de HIV/química | pt_BR |
| DeCS | HIV-1/crescimento & desenvolvimento | pt_BR |
| DeCS | Humanos | pt_BR |
| DeCS | Nanoconjugados/ultraestrutura | pt_BR |
| DeCS | Tamanho da Partícula | pt_BR |
| DeCS | Peptídeos/síntese química | pt_BR |
| DeCS | Ligação Proteica | pt_BR |
| DeCS | Triazóis/síntese química | pt_BR |
| DeCS | Inativação de Vírus/efeitos de drogas | pt_BR |
| DeCS | Internalização do Vírus/efeitos de drogas | pt_BR |
| Data de embargo | 2016-02-29 | |
