Structure-guided design of a novel class of benzyl-sulfonate inhibitors for influenza virus neuraminidase
- Author(s)
- Platis, D; Smith, BJ; Huyton, T; Labrou, NE;
- Journal Title
- BIOCHEMICAL JOURNAL
- Publication Type
- Journal Article
- Abstract
- Influenza NA (neuraminidase) is an antiviral target of high pharmaceutical interest because of its essential role in cleaving sialic acid residues from cell surface glycoproteins and facilitating release of virions from infected cells. The present paper describes the use of structural information in the progressive design from a lead binding ion (a sulfate) to a potent submicromolor inhibitor (K-i 0.13 mu M). Structural information derived from the X-ray structure of an NA complexed with several sulfate ions, in combination with results derived from affinity labelling and molecular modelling studies, was used to guide design of potent sulfonic acid-based inhibitors. These inhibitors are structural fragments of the polysulfonate triazine dye Cibacron Blue 3GA and represent novel lead scaffolds for designing non-carbohydrate inhibitors for influenza neuraminidases.
- Publisher
- PORTLAND PRESS LTD
- Keywords
- GLUTATHIONE-S-TRANSFERASE; LIVER ALCOHOL-DEHYDROGENASE; BIOMIMETIC DYE-LIGANDS; CIBACRON BLUE F3GA; AFFINITY ADSORBENTS; PANDEMIC INFLUENZA; DRUG DESIGN; BINDING; HEMAGGLUTININ; ZANAMIVIR
- Publisher's Version
- https://doi.org/10.1042/BJ20060447
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-10-15 12:00:00