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Advances in biocatalytic and chemoenzymatic synthesis of nucleoside analogues.

Cosgrove, Sebastian C.; Miller, Gavin J.

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Abstract

INTRODUCTION: Nucleoside analogues represent a cornerstone of achievement in drug discovery, rising to prominence particularly in the fields of antiviral and anticancer discovery over the last 60 years. Traditionally accessed using chemical synthesis, a paradigm shift to include the use of biocatalytic synthesis is now apparent.

AREAS COVERED: Herein the authors discuss the recent advances using this technology to access nucleoside analogues. Two key aspects are covered, the first surrounding methodology concepts, effectively using enzymes to access diverse nucleoside analogue space and also for producing key building blocks. The second focuses on the use of biocatalytic cascades for de novo syntheses of nucleoside analogue drugs. Finally, recent advances in technologies for effecting enzymatic nucleoside synthesis are considered, chiefly immobilisation and flow.

EXPERT OPINION: Enzymatic synthesis of nucleoside analogues is maturing but has yet to usurp chemical synthesis as a first-hand synthesis technology, with scalability and substrate modification primary issues. Moving forward, tandem approaches that harness expertise across molecular microbiology and chemical synthesis will be vital to unlocking the potential of nucleoside analogues.

Journal Article Type Review
Acceptance Date Feb 4, 2022
Online Publication Date Feb 17, 2022
Publication Date Feb 8, 2022
Publicly Available Date Mar 28, 2024
Journal Expert Opinion on Drug Discovery
Print ISSN 1746-0441
Publisher Taylor and Francis
Peer Reviewed Peer Reviewed
Volume 17
Issue 4
Pages 355-364
DOI https://doi.org/10.1080/17460441.2022.2039620
Keywords Nucleoside analogue; biocatalysis; enzymes; chemoenzymatic synthesis
Publisher URL https://doi.org/10.1080/17460441.2022.2039620

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