Sustainable Flow-Synthesis of (Bulky) Nucleoside Drugs by a Novel and Highly Stable Nucleoside Phosphorylase Immobilized on Reusable Supports.

ABSTRACT: The continuous synthesis of valuable nucleoside drugs was achieved in up to 99 % conversion by using a novel halotolerant purine nucleoside phosphorylase from Halomonas elongata (HePNP). HePNP showed an unprecedented tolerance to DMSO, usually required for substrate solubility, and could be immobilized on agarose microbeads through disulfide bonds, via a genetically fused Cystag. This covalent yet reversible binding chemistry showcased the reusability of agarose microbeads in a second round of enzyme immobilization with high reproducibility, reducing waste and increasing the sustainability of the process. Finally, the flow synthesis of a Nelarabine analogue (6-O-methyl guanosine) was optimized to full conversion on a 10 mm scale within 2 min residence time, obtaining the highest space-time

SUBMITTER: Benitez-Mateos AI 

PROVIDER: S-EPMC9298701 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature