Identification of biologically active, HIV TAR RNA-binding small molecules using small molecule microarrays.

ABSTRACT: Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies to find RNA-binding molecules have identified highly charged compounds or aminoglycosides that commonly have modest selectivity. Here we demonstrate a strategy to screen a large unbiased library of druglike small molecules in a microarray format against an RNA target. This approach has enabled the identification of a novel chemotype that selectively targets the HIV transactivation response (TAR) RNA hairpin in a manner not dependent on cationic charge. Thienopyridine 4 binds to and stabilizes the TAR hairpin with a Kd of 2.4 μM. Structure-activity relationships demonstrate that this compound achieves activity through hydro

SUBMITTER: Sztuba-Solinska J 

PROVIDER: S-EPMC4227816 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature