Sustainable flow‐synthesis of (bulky)nucleoside drugs by a novel and highly stable nucleoside phosphorylase immobilized on reusable supports

Benitez Mateos, Ana I.; Paradisi, Francesca (2022). Sustainable flow‐synthesis of (bulky)nucleoside drugs by a novel and highly stable nucleoside phosphorylase immobilized on reusable supports. ChemSusChem, 15(1), e202102030. Wiley-VCH 10.1002/cssc.202102030

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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 yield (89 g L -1 h -1 ) reported to date. The cost-efficiency of the system was further enhanced by a catch-and-release strategy that allowed to recover and recirculate the excess of sugar donor from the downstream water waste.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Benitez Mateos, Ana Isabel, Paradisi, Francesca

Subjects:

500 Science > 540 Chemistry

ISSN:

1864-5631

Publisher:

Wiley-VCH

Funders:

[185] University of Bern: Seal of Excellence Fund ; [4] Swiss National Science Foundation

Projects:

[UNSPECIFIED] BIOORPHANDRUGS
[UNSPECIFIED] 200021_192274

Language:

English

Submitter:

Francesca Paradisi

Date Deposited:

15 Nov 2021 14:16

Last Modified:

05 Dec 2022 15:54

Publisher DOI:

10.1002/cssc.202102030

PubMed ID:

34726353

BORIS DOI:

10.48350/160633

URI:

https://boris.unibe.ch/id/eprint/160633

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