STRUCTURE-BASED DRUG DESIGN METHODS FOR IDENTIFYING D-ALA-D-ALA LIGASE INHIBITORS AS ANTIBACTERIAL DRUGS
摘要
The invention is based on the discovery that certain small molecules can bin d to the ATP binding site of D-Ala-D-Ala ligase, even in the absence of the enzyme's substrate, and can cause a conformational change in the enzyme structure similar to that which occurs upon binding of ATP and substrate to the enzyme. Without wishing to be bound by any theory, it is believed that such a conformational change is required for either activation or inhibition of the enzyme. The information obtained from this discovery has enabled identification of key interactions in the active site of the enzyme, as well as the design and opimization of inhibitors.
申请公布号
CA2451837(A1)
申请公布日期
2003.01.09
申请号
CA20022451837
申请日期
2002.06.28
申请人
ESSENTIAL THERAPEUTICS, INC.;PLIVA D.D.
发明人
ALI, JANID A.;GRIFFITH, JAMES P.;ALA, PAUL J.;MOE, SCOTT T.;FAERMAN, CARLOS H.;PEROLA, EMANUELE;CONNELLY, PATRICK R.;MAGEE, ANDREW S.;NAVIA, MANUEL A.