1275608-16-6Relevant articles and documents
Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity
Tari, Leslie W.,Trzoss, Michael,Bensen, Daniel C.,Li, Xiaoming,Chen, Zhiyong,Lam, Thanh,Zhang, Junhu,Creighton, Christopher J.,Cunningham, Mark L.,Kwan, Bryan,Stidham, Mark,Shaw, Karen J.,Lightstone, Felice C.,Wong, Sergio E.,Nguyen, Toan B.,Nix, Jay,Finn, John
, p. 1529 - 1536 (2013/03/14)
The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity.
