# 3′-O-β-Glucosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase

## TL;DR

This paper explores using a bacterial enzyme to glycosylate nucleoside analogues, improving their potential as drugs.

## Contribution

The study demonstrates the promiscuity of AvpGT in glycosylating various nucleoside analogues on a scalable level.

## Key findings

- AvpGT glycosylated 15 of 21 nucleoside analogues tested.
- 12 nucleosides were glycosylated in 39–91% yields on ≥25 μmol scale.
- Four current therapeutics were successfully modified using this method.

## Abstract

Nucleoside analogue therapeutics have a proven capability within drug discovery as antiviral and antineoplastic agents. However, their efficacy can be limited by poor cellular uptake, off target toxicity and low bioavailability. Glycosylation of pharmaceutical agents/natural products represents a strategically simple method to modulate pharmacological profiles. Herein, we explore biocatalytic glycosylation of nucleoside analogues. The activity of the nucleoside-specific 3′-O-glycosyltransferase AvpGT from Streptomyces sp. AVP053U2 is investigated toward a panel of both natural and clinically relevant purine and pyrimidine nucleoside analogues. AvpGT demonstrates broad substrate promiscuity, with glycosylation observed by HILIC-MS for 15 of 21 nucleosides tested. Of these, 12 nucleosides were successfully glycosylated on ≥25 μmol scale in 39–91% isolated yields, including four current therapeutics.

Biocatalytic glycosylation of nucleoside analogues using a promiscuous nucleoside-specific 3′-O-glycosyltransferase, AvpGT.