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Functionalizing Nucleic Acid Nanostructures by Targeting Abasic Sites in DNA Modules with Amiloride Derivatives

Abstract

DNA and RNA have become of interest in nanotechnology applications due to nucleic acids’ ability to encode folding and programmable self-assembly primarily through base paring. A versatile kit of robust polygonal nanoshapes self-assembling from DNA and RNA modules provide a novel framework to integrate a combination of RNA motifs as architectural joints and DNA building blocks as functional modules. The RNA-DNA hybrid nanostructure provides the platform for application in molecular recognition, sensor and catalyst development in addition to protein interaction studies. The design, assembly and characterization of RNA-DNA hybrid structures has been established, methods for chemical modification of DNA components are being explored.

DNA components of RNA-DNA nanostructures were modified to carry diverse functional groups by targeting abasic sites in DNA helices with a selective ligand, amiloride. Amiloride was explored as a possible non-covalent ligand that targets abasic sites within DNA duplexes. Amiloride derivatives were synthesized with various side chain linkers and substituents to test binding within RNA-DNA hybrid nanostructures and expand diverse application of DNA modules.

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