We have designed and synthesized new broad spectrum inibitors of beta-lactamases acting on class A, C and D. X-ray structure has provided structural insight enabling further optimization of lead compound.
We reported the high resolution crystal structures of MurD in complexes with two novel inhibitors designed to mimic the transition state of the reaction, which contain either the D-Glu or the L-Glu moiety. The binding modes of N-sulfonyl-D-Glu and N-sulfonyl-L-Glu derivatives were also characterized kinetically.
The main structural feature of direct thrombin inhibitor LK-732 responsible for the appropriate interaction at the thrombin active site is a strong basic group. A possibility that a strong basic group of LK-732 might contribute to the mast cell degranulation effect and consequent reduction of tracheal air flow (TAF) and fall of mean arterial blood pressure (MAP) in rats was investigated.
The strategy of research towards new antimicrobial agents has been discussed and proposed.
A series of naphthalene-N-sulfonyl-d-glutamic acid derivatives are novel MurD ligase inhibitors with moderate affinity.We performed an NMR study including transfer NOE to determine the ligand bound conformation, as well as saturation transfer difference experiments to obtain ligand epitope maps.