Two-pronged approach to RNA binding

摘要

The prospect of using RNA as a drug target is of great interest to scientists, but due to its complex structure, designing ligands that bind to it is challenging. Scientists from the University of North Carolina at Chapel Hill, US, have overcome these difficulties by combining two weak ligands to make an RNA-binding conjugate that is far better than the sum of its parts.rn'Although cooperative binding has been explored in the past,' says Marcey Waters, who carried out the research with Lauren Cline, 'our system is the first example of coupling a sequence-selective threading intercalator with a (3-hairpin peptide that is known to selectively bind unpaired bases.' The result is a system that simultaneously targets both the single- and double-stranded regions of RNA. While thernintercalator threads between two G-C base pairs adjacent to bulges in the RNA, the peptide targets exposed bases in the RNA's single-stranded loops and bulges, resulting in binding that is at least 30 times more favourable than for either unit alone.