High Affinity Binding of N2-Modified Guanine Derivatives Significantly Disrupts the Ligand Binding Pocket of the Guanine Riboswitch.

ABSTRACT: Riboswitches are important model systems for the development of approaches to search for RNA-targeting therapeutics. A principal challenge in finding compounds that target riboswitches is that the effector ligand is typically almost completely encapsulated by the RNA, which severely limits the chemical space that can be explored. Efforts to find compounds that bind the guanine/adenine class of riboswitches with a high affinity have in part focused on purines modified at the C6 and C2 positions. These studies have revealed compounds that have low to sub-micromolar affinity and, in a few cases, have antimicrobial activity. To further understand how these compounds interact with the guanine riboswitch, we have performed an integrated structural and functional analysis of representative guanin

SUBMITTER: Matyjasik MM 

PROVIDER: S-EPMC7287874 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature