Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA.

ABSTRACT: The preQ₁ cIass-I riboswitch aptamer can utilize 7-aminomethyl-7-deazaguanine (preQ₁) ligands that are equipped with an electrophilic handle for the covalent attachment of the ligand to the RNA. The simplicity of the underlying design of irreversibly bound ligand-RNA complexes has provided a new impetus in the fields of covalent RNA labeling and RNA drugging. Here, we present short and robust synthetic routes for such reactive preQ₁ and (2,6-diamino-7-aminomethyl-7-deazapurine) DPQ₁ ligands. The readily accessible key intermediates of preQ₀ and DPQ₀ (both bearing a nitrile moiety instead of the aminomethyl group) were reduced to the corresponding 7-formyl-7-deazapurine counterparts. These readily undergo reductive amination

SUBMITTER: Flemmich L 

PROVIDER: S-EPMC11897656 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature