Demonstration that Small Molecules can Bind and Stabilize Low-abundance Short-lived RNA Excited Conformational States.

ABSTRACT: Many promising RNA drug targets have functions that require the formation of RNA-protein complexes, but inhibiting RNA-protein interactions can prove difficult using small molecules. Regulatory RNAs have been shown to transiently form excited conformational states (ESs) that remodel local aspects of secondary structure. In some cases, the ES conformation has been shown to be inactive and to be poorly recognized by protein binding partners. In these cases, specifically targeting and stabilizing the RNA ES using a small molecule provides a rational structure-based strategy for inhibiting RNA activity. However, this requires that a small molecule discriminates between two conformations of the same RNA to preferentially bind and stabilize the short-lived low-abundance ES relative to the long-l

SUBMITTER: Ganser LR 

PROVIDER: S-EPMC7054137 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature