ATP competitive inhibitors of D-alanine-D-alanine ligase based on protein kinase inhibitor scaffolds.
Basic Information
ID: ALA1140982
Journal: Bioorg Med Chem
Title: ATP competitive inhibitors of D-alanine-D-alanine ligase based on protein kinase inhibitor scaffolds.
Authors: Triola G, Wetzel S, Ellinger B, Koch MA, Hübel K, Rauh D, Waldmann H.
Abstract: D-Alanine-D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics. Here, we describe a new approach to identify new inhibitor scaffolds for DDl based on similarity in the ATP binding region of different kinases and DDl. After an initial screening of several protein kinase inhibitors, we found that the Brutons's tyrosine kinase inhibitor LFM-A13, an analog of the Leflunomide metabolite A771726, inhibits DDl with a K(i) of 185 microM. A series of malononitrilamide and salicylamide derivatives of LFM-A13 has been synthesized to confirm the validity of this scaffold as an inhibitor of DDl.
CiteXplore: 18321716
DOI: 10.1016/j.bmc.2008.02.046
Patent ID: ┄