Non-antibiotic Small-Molecule Regulation of DHFR-Based Destabilizing Domains In Vivo.

ABSTRACT: The E. coli dihydrofolate reductase (DHFR) destabilizing domain (DD), which shows promise as a biologic tool and potential gene therapy approach, can be utilized to achieve spatial and temporal control of protein abundance in vivo simply by administration of its stabilizing ligand, the routinely prescribed antibiotic trimethoprim (TMP). However, chronic TMP use drives development of antibiotic resistance (increasing likelihood of subsequent infections) and disrupts the gut microbiota (linked to autoimmune and neurodegenerative diseases), tempering translational excitement of this approach in model systems and for treating human diseases. Herein, we identified a TMP-based, non-antibiotic small molecule, termed 14a (MCC8529), and tested its ability to control multiple DHFR-base

SUBMITTER: Peng H 

PROVIDER: S-EPMC6804886 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature