Target-Directed Dynamic Combinatorial Chemistry Affords Binders of Mycobacterium tuberculosis IspE.

ABSTRACT: In the search for new antitubercular compounds, we leveraged target-directed dynamic combinatorial chemistry (tdDCC) as an efficient hit-identification method. In tdDCC, the target selects its own binders from a dynamic library generated in situ, reducing the number of compounds that require synthesis and evaluation. We combined a total of 12 hydrazides and six aldehydes to generate 72 structurally diverse N-acylhydrazones. To amplify the best binders, we employed anti-infective target 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) from Mycobacterium tuberculosis (Mtb). We successfully validated the use of tdDCC as hit-identification method for IspE and optimized the analysis of tdDCC hit determination. From the 72 possible N-acylhydrazone

SUBMITTER: Braun-Cornejo M 

PROVIDER: S-EPMC11391541 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature