Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. (Articolo in rivista) (literal)

Anno

• 2010-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1016/j.antiviral.2010.03.008 (literal)

Alternative label

• Samuele A a, Crespan E a, Vitellaro S a, Monforte AM b, Logoteta P b, Chimirri A b, Maga G a. (2010)
  Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation.
  in Antiviral research (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Samuele A a, Crespan E a, Vitellaro S a, Monforte AM b, Logoteta P b, Chimirri A b, Maga G a. (literal)

Pagina inizio

• 268 (literal)

Pagina fine

• 275 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 86 (literal)

Rivista

• Antiviral research (Rivista)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• aDepartment of DNA Enzymology and Molecular Virology, Institute of Molecular Genetics-National Research Council, IGM-CNR, via Abbiategrasso 207, 27100 Pavia, Italy b Pharmaceutic and Chemistry Department, University of Messina, Viale Annunziata 98168, Messina, Italy (literal)

Titolo

• Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. (literal)

Abstract

• Novel benzimidazol-2-one non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been recently identified, through rational structure-based molecular modeling and docking approaches, as highly effective inhibitors of the wild type and drug-resistant HIV-1 reverse transcriptase (RT). These compounds also showed potent anti-HIV activities against viral strains, superior to the clinically approved NNRTI efavirenz. However, they were still of limited efficacy towards the K103N mutant. Here we report a detailed enzymatic analysis elucidating the molecular mechanism of interaction between benzimidazol-2-one derivatives and the K103N mutant RT. The loss of potency of these molecules towards the K103N RT was specifically due to a reduction of their association rate to the enzyme. Unexpectedly, these compounds showed a strongly reduced dissociation rate from the K103N mutant, as compared to the wild type enzyme, suggesting that, once occupied by the drug, the mutated binding site could achieve a more stable interaction with these molecules. The characterization of this slow binding-tight binding mutant-specific mechanism of interaction may pave the way to the design of more effective new generation benzimidazol-2-one NNRTIs with promising drug resistant profile and minimal toxicity. Copyright © 2010. Published by Elsevier B.V. (literal)

Prodotto di

• Institute of molecular genetics (IGM) (Istituto)
• Sviluppo e meccanismo d'azione di analoghi nucleotidici e nucleosidici come composti antiproliferativi e antivirali : nuovi composti e nuovi bersagli per la terapia (ME.P04.004.001) (Modulo)

Autore CNR

• EMMANUELE CRESPAN (Persona)
• ALBERTA SAMUELE (Unità di personale interno)
• GIOVANNI MAGA (Unità di personale interno)

Insieme di parole chiave

• Parole chiave di "Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation." (Insieme di parole chiave)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)
• Sviluppo e meccanismo d'azione di analoghi nucleotidici e nucleosidici come composti antiproliferativi e antivirali : nuovi composti e nuovi bersagli per la terapia (ME.P04.004.001) (Modulo)

Autore CNR di

• GIOVANNI MAGA (Unità di personale interno)
• EMMANUELE CRESPAN (Persona)
• ALBERTA SAMUELE (Unità di personale interno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Antiviral research (Rivista)

Insieme di parole chiave di

• Parole chiave di "Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation." (Insieme di parole chiave)