SHAPE-based chemical probes for studying preQ₁-RNA interactions in living bacteria.

ABSTRACT: Interrogating RNA-small molecule interactions inside cells is critical for advancing RNA-targeted drug discovery. In particular, chemical probing technologies that both identify small molecule-bound RNAs and define their binding sites in the complex cellular environment will be key for establishing the on-target activity necessary for successful hit-to-lead campaigns. Using the small molecule metabolite preQ₁ and its cognate riboswitch RNA as a model, herein we describe a chemical probing strategy for filling this technological gap. Building on well-established RNA acylation chemistry employed by in vivo click selective 2'-hydroxyl acylation analyzed by primer extension (icSHAPE) probes, we developed an icSHAPE-based preQ₁ probe that retains biological activity

SUBMITTER: Franceschi JAR 

PROVIDER: S-EPMC12330648 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature