Synthesis of Glycine-containing Nucleotide Analog for Developing a Novel Chemo-enzymatic DNA Labeling Method

Abstract

Nucleic acid functionalizing technologies greatly aid in understanding the structure and functioning of nucleic acids. A chemoselective reaction has become one of the most powerful techniques for labeling nucleic acids in recent years. However, only a few qualify as bioorthogonal reactions that enable the labeling of nucleic acids in vitro and cellular environments. Therefore, the development of new nucleic acid labeling techniques remains a high priority. In this project, we intend to develop a chemoselective nucleic acid labeling technique by using glycine-modified nucleotide. The method generates an imine that reacts with an aldehyde primed with a tag to deliver an aminoalcohol. The formation of a latent electrophile followed by glycine residue-specific generation of nucleophilic intermediate is the key to attain chemoselectivity. The symmetric bis-aldehyde reagent can be used to install a variety of affinity tags and biophysical probes for potential application in the analysis of nucleic acids.