METHODS OF STRUCTURE-based DESIGN OF MEDICINES FOR IDENTIFICATION OF D-Ala-D-Ala-LIGASE INHIBITORS AS ANTIBACTERIAL DRUGS

摘要

The invention is based on the discovery that certain small molecules can bind to the ATP-binding site of D-Ala-D-Ala-ligase even in the absence of an enzyme substrate and can cause a conformational change in the structure of the enzyme, similar to that which occurs during the binding of ATP and substrate with enzyme. Not limited to any theory, it is assumed that such a conformational change is required either to activate or to inhibit the enzyme. Information obtained on the basis of this discovery made it possible to identify key interactions in the active site of the enzyme, as well as the design and optimization of inhibitors. The international search report was published 2003.02.20.