Small molecules reveal differential shifts in stability and protein binding for G-quadruplex RNA.

ABSTRACT: The potential of therapeutically targeting RNA with small molecules continues to grow yet progress is hindered by difficulties in determining specific mechanisms of action, including impacts on RNA-protein binding. RNA G-quadruplexes (rGQs) are a particularly promising target due to their range of biological functions, structural stability, and hydrophobic surfaces, which promote small molecule and protein interactions alike. Challenges arise due to 1) the low structural diversity among rGQs, thereby limiting binding selectivity, and 2) a lack of knowledge regarding how small molecules can manipulate rGQ-protein binding on a global scale. We first leveraged a small molecule library privileged for RNA tertiary structures that displayed differential binding to rGQs based on loop length, cons

SUBMITTER: Martyr JG 

PROVIDER: S-EPMC11844376 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature