Structure-guided design of a novel class of benzyl-sulfonate inhibitors for influenza virus neuraminidase

被引:13
作者
Platis, Dimitris
Smith, Brian J.
Huyton, Trevor
Labrou, Nikolaos E.
机构
[1] Agr Univ Athens, Dept Agr Biotechnol, Lab Enzyme Technol, Athens 11855, Greece
[2] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
关键词
benzyl-sulfonate inhibitor; Cibacron Blue 3GA (CB3GA); influenza; neuraminidase (NA); structure-guided design;
D O I
10.1042/BJ20060447
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:215 / 223
页数:9
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