Correlating Drug-Target Residence Time and Post-antibiotic Effect: Insight into Target Vulnerability.

ABSTRACT: Target vulnerability correlates the level of drug-target engagement required to generate a pharmacological response. High vulnerability targets are those that require only a relatively small fraction of occupancy to achieve the desired pharmacological outcome, whereas low vulnerability targets require high levels of engagement. Here, we demonstrate that the slope of the correlation between drug-target residence time and the post-antibiotic effect (PAE) can be used to define the vulnerability of bacterial targets. For macrolides, a steep slope is observed between residence time on the E. coli ribosome and the PAE, indicating that the ribosome is a highly vulnerable drug target. The analysis of the residence time-PAE data for erythromycin, azithromycin, spiramycin, and telithromycin u

SUBMITTER: Davoodi S 

PROVIDER: S-EPMC7150629 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature