Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1.
Click chemistry
Crystal structure
Influenza neuraminidase
Oseltamivir
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
01
04
2019
revised:
09
05
2019
accepted:
16
05
2019
pubmed:
28
5
2019
medline:
2
9
2020
entrez:
27
5
2019
Statut:
ppublish
Résumé
This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported K
Identifiants
pubmed: 31128993
pii: S0968-0896(19)30535-8
doi: 10.1016/j.bmc.2019.05.024
pii:
doi:
Substances chimiques
Oseltamivir
20O93L6F9H
Neuraminidase
EC 3.2.1.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2935-2947Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.