Discovery of PqsE Thioesterase Inhibitors for <i>Pseudomonas aeruginosa</i> Using DNA-Encoded Small Molecule Library Screening.

ABSTRACT: Pseudomonas aeruginosa is a leading cause of hospital-acquired infections in the United States. PqsE, a thioesterase enzyme, is vital for virulence of P. aeruginosa, making PqsE an attractive target for inhibition. Neither the substrate nor the product of PqsE catalysis has been identified. A library of 550 million DNA-encoded drug-like small molecules was screened for those that bind to the purified PqsE protein. The structures of the bound molecules were identified by high throughput sequencing of the attached DNA barcodes. Putative PqsE binders with the strongest affinity features were examined for inhibition of PqsE thioesterase activity in vitro. The most potent inhibitors were resynthesized off DNA and examined for the ability to alter PqsE thermal melting and fo

SUBMITTER: Valastyan JS 

PROVIDER: S-EPMC7036018 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature