# Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates

## TL;DR

This paper reviews the synthesis and properties of modified nucleoside triphosphates with altered phosphate groups, highlighting their use in molecular biology.

## Contribution

The paper systematically analyzes synthesis methods and applications of α-phosphate-modified nucleoside triphosphates.

## Key findings

- Modified triphosphates with heteroatoms like sulfur or selenium are nuclease resistant.
- These modified triphosphates can be recognized and incorporated into DNA or RNA by polymerases.
- They serve as tools in studies of polymerase mechanisms and SELEX experiments.

## Abstract

This review article is focused on the progress made in the synthesis of 5′-α-P-modified nucleoside triphosphates (α-phosphate mimetics). A variety of α-P-modified nucleoside triphosphates (NTPαXYs, Y = O, S; X = S, Se, BH3, alkyl, amine, N-alkyl, imido, or others) have been developed. There is a unique class of nucleoside triphosphate analogs with different properties. The main chemical approaches to the synthesis of NTPαXYs are analyzed and systematized here. Using the data presented here on the diversity of NTPαXYs and their synthesis protocols, it is possible to select an appropriate method for obtaining a desired α-phosphate mimetic. Triphosphates’ substrate properties toward nucleic acid metabolism enzymes are highlighted too. We reviewed some of the most prominent applications of NTPαXYs including the use of modified dNTPs in studies on mechanisms of action of polymerases or in systematic evolution of ligands by exponential enrichment (SELEX). The presence of heteroatoms such as sulfur, selenium, or boron in α-phosphate makes modified triphosphates nuclease resistant. The most distinctive feature of NTPαXYs is that they can be recognized by polymerases. As a result, S-, Se-, or BH3-modified phosphate residues can be incorporated into DNA or RNA. This property has made NTPαXYs a multifunctional tool in molecular biology. This review will be of interest to synthetic chemists, biochemists, biotechnologists, or biologists engaged in basic or applied research.