Programming inactive RNA-binding small molecules into bioactive degraders.

ABSTRACT: Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded RNA structures. Mapping these interaction landscapes across the human transcriptome defined structure-activity relationships. Although RNA-binding compounds that bind to functional sites were expected to elicit a biological response, most identified interactions were predicted to be biologically inert as they bind elsewhere. We reasoned that, for such cases, an alternative strategy to modulate RNA biology is to cleave the target through a ribonucl

SUBMITTER: Tong Y 

PROVIDER: S-EPMC10232370 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature