Tethering in RNA: an RNA-binding fragment discovery tool.
Tethering has been extensively used to study small molecule interactions with proteins through reversible disulfide bond forming reactions to cysteine residues. We describe the adaptation of Tethering to the study of small molecule binding to RNA using a thiol-containing adenosine analog (ASH). Among 30 disulfide-containing small molecules screened for efficient Tethering to ASH-bearing RNAs derived from pre-miR21, a benzotriazole-containing compound showed prominent adduct formation and selectivity for one of the RNAs tested. The results of this screen demonstrate the viability of using thiol-modified nucleic acids to discover molecules with binding affinity and specificity for the purpose of therapeutic compound lead discovery.
Department of Chemistry, University of California, One Shields Ave, Davis, CA 95616, USA. ktutran@ucdavis.edu.
Kiet
K
Tran
Small Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA. Michelle.Arkin@ucsf.edu.
Michelle R
MR
Arkin
Department of Chemistry, University of California, One Shields Ave, Davis, CA 95616, USA. pabeal@ucdavis.edu.
Peter A
PA
Beal
D001665:Binding Sites; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism*
D004220:Disulfides; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D004364:Pharmaceutical Preparations; D012313:RNA