Author/Authors :
Paul W. Smith، نويسنده , , Steven L. Sollis، نويسنده , , Peter D. Howes، نويسنده , , Peter C. Cherry، نويسنده , , Kevin N. Cobley، نويسنده , , Helen Taylor، نويسنده , , Andrew R. Whittington، نويسنده , , Jan Scicinski، نويسنده , , Richard C. Bethell، نويسنده , , T. G. Neil Taylor، نويسنده , , Tadeusz Skarzynski، نويسنده , , Anne Cleasby، نويسنده , , Oncar Singh، نويسنده , , Alan Wonacott، نويسنده , , Sudhir Kumar and Jose Varghese ، نويسنده , , Peter Colman، نويسنده ,
Abstract :
The structure-activity relationships of a series of 4-amino and guanidino-4H-pyran-2-carboxylic acid 6-carboxamides are described. These compounds represent a new class of inhibitor of influenza sialidases and are particularly active against influenza A sialidase. The binding of the N-phenethyl-N-propylamide 41 to influenza A and B sialidases has been investigated using X-ray crystallography and molecular dynamics simulations. Our results suggest that formation of a hitherto unobserved intramolecular salt bridge within the enzymes may account for the observed activity and selectivity of the series.
