1092117-40-2Relevant articles and documents
Novel naphthalene-N-sulfonyl-D-glutamic acid derivatives as inhibitors of MurD, a key peptidoglycan biosynthesis enzyme
Humljan, Jan,Kotnik, Miha,Contreras-Martel, Carlos,Blanot, Didier,Urleb, Uro?,Dessen, Andréa,?olmajer, Tom,Gobec, Stanislav
supporting information; experimental part, p. 7486 - 7494 (2009/11/30)
Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships. The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transitionstate analogues, displayed IC50 values ranging from 80 to 600 μM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.
