Properties and reactivity of nucleic acids relevant to epigenomics, transcriptomics, and therapeutics

Abstract

Developments in epigenomics, toxicology, and therapeutic nucleic acids all rely on a precise understanding of nucleic acid properties and chemical reactivity. In this review we discuss the properties and chemical reactivity of each nucleobase and attempt to provide some general principles for nucleic acid targeting or engineering. For adenine-thymine and guaninecytosine base pairs, we review recent quantum chemical estimates of their Watson-Crick interaction energy, - stacking energies, as well as the nuclear quantum effects on tautomerism. Reactions that target nucleobases have been crucial in the development of new sequencing technologies and we believe further developments in nucleic acid chemistry will be required to deconstruct the enormously complex transcriptome.

A Benzophenone‐Based Photocaging Strategy for the N7 Position of Guanosine

“…First, we explored the chemical photocaging of guanosine 1 using the well‐known ortho ‐nitrobenzyl (ONB) group as well as para ‐nitrobenzyl (PNB) as negative control. The N7 of guanosine is the most potent nucleophile in DNA and RNA . However, although N7G methylation was used in Maxam Gilbert sequencing, the chemical modification of N7 has not been exploited to manipulate and control interactions by orthogonal triggers such as light.…”

Highly accurate equilibrium structure of the C2h symmetric N1‐to‐O2 hydrogen‐bonded uracil‐dimer

“…Nucleobases are quintessential components of life and their structures and molecular complexes are of high interest for both the experimental and computational community. Interaction energies for intermolecular (model) complexes, that is, stacking of bases or hydrogen‐bonded complexes, have been thoroughly investigated over the last decade with a multitude of different computational methods . For many of these model complexes the interaction energies are reliably known up to tenths of kcal·mol −1 accuracy and beyond.…”

Genomic Studies Reveal New Aspects of the Biology of DNA Damaging Agents

“…[11] An umber of methods exist for the genome-wide analysis of photoproducts [12] and other types of DNA damage (and these have revealed interesting aspects of damage selectivity), buth erein we focus on the XR-Seq and cisplatin-Seq techniques because theseh ave contributed most to refining the models for mutation vulnerability. General technological innovations in DNA and RNA sequencing over the past 20 years are an essential part of sequencing DNA lesions,b ut more recent innova-tions for in vitro chemical sequencing, as well as epigenome and epitranscriptome sequencing, have finally allowedu st o achieves ingle nucleotide resolution in determining sites of DNA damage genome wide.…”