High‐Fidelity Recognition of RNA: Solution Structure of a DNA:RNA Hybrid Duplex with a Molecular Cap. Issue 17 (16th October 2014)

• Record Type: Journal Article
• Authors: Gerlach, Claudia; Claasen, Birgit; Richert, Clemens
• Is Part Of: Chembiochem. Volume 15:Issue 17(2014)
• Page Start: 2584
• Page End: 2589
• Publication Date: 2014-10-16
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402409
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Binding RNA targets, such as microRNAs, with high fidelity is challenging, particularly when the nucleobases to be bound are located at the terminus of the duplex between probe and target. Recently, a peptidyl chain terminating in a quinolone, called ogOA, was shown to act as a cap that enhances affinity and fidelity for RNAs, stabilizing duplexes with Watson–Crick pairing at their termini. Here we report the three‐dimensional structure of an intramolecular complex between a DNA strand featuring the ogOA cap and an RNA segment, solved by NMR and restrained torsion angle molecular dynamics. The quinolone stacks on the terminal base pair of the hybrid duplex, positioned by the peptidyl chain, whose prolinol residue induces a sharp bend between the 5′ terminus of the DNA chain and the glycine linked to the oxolinic acid residue. The structure explains why canonical base pairing is favored over hard‐to‐suppress mismatched base combinations, such as T:G and A:A, and helps to design improved high‐fidelity probes for RNA.</p> </abstract>