Nucleic Acids -Chemistry and Applications

Abstract

The year 2013 marked the 60th anniversary of the elucidation of the structure of the DNA double helix by Watson and Crick.(1) Its molecular structure comprises a backbone of repetitive units of sugar (2′-deoxyribose)phosphate, with each sugar bearing one of the four nucleobases (A/G/C/T) through glycosidic linkages. The double helical superstructure of DNA spawned the understanding of the molecular basis of life in terms of how this genetic code could both decode and propagate. However, what was unforeseen was how the molecular and supramolecular structure of DNA would lead chemists to design future drugs, diagnostics, and new materials through explorations of chemical space in both modified DNA and RNA structures as well as its expanded functionality. Ranging from the realization of antisense-based nucleic acid analogues to covalent conjugation of functional ligands and the explosion of DNA as a nanoscale construction material, the most recent decades have seen DNA evolve from just “genetic” material to a “generic” material for several applications. Organic chemistry has been central to this evolution, from enabling the affordable, custom synthesis of any DNA/RNA sequence to the development of rapid and super-efficient methods to sequence DNA. The brisk pace of genetic engineering, chemical biology, bionanotechnology, and synthetic biology rests heavily on the development of enabling chemistry. This virtual issue seeks to highlight the frequently overlooked role of exciting chemistry underlying nucleic acid biology. We have highlighted 25 exciting papers from J. Org. Chem., Org. Lett., and J. Am. Chem. Soc. published between January 2012 and November 2013, under four broad categories—chemical modifications and DNA/RNA analogues, gene silencing and delivery methods, fluorescent nucleic acids, and self-assembly-derived DNA materials.