Tethering in RNA: An RNA-Binding Fragment Discovery Tool

Molecules

Kiet Tran²  Michelle R. Arkin¹  Peter A. Beal²  Mahesh K. Lakshman³ 

[1] Small Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA; E-Mail:;Department of Chemistry, University of California, One Shields Ave, Davis, CA 95616, USA; E-Mail:;Department of Chemistry, University of California, One Shields Ave, Davis, CA 95616, USA; E-Mail

关键词: Tethering;    miRNA;    nucleoside analog;   

DOI  :  10.3390/molecules20034148

来源: mdpi

【 摘 要 】

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 (A_SH). Among 30 disulfide-containing small molecules screened for efficient Tethering to A_SH-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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.