Nucleoside analogues (NAs) are among the most successful small-molecule classes in the fight against cancer and viral infections. Their importance has recently been further underlined by the approval of sofosbuvir for the treatment of hepatitis C virus infections and by developments related to the c...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Académie des sciences
2025-03-01
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| Series: | Comptes Rendus. Chimie |
| Subjects: | |
| Online Access: | https://comptes-rendus.academie-sciences.fr/chimie/articles/10.5802/crchim.388/ |
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| Summary: | Nucleoside analogues (NAs) are among the most successful small-molecule classes in the fight against cancer and viral infections. Their importance has recently been further underlined by the approval of sofosbuvir for the treatment of hepatitis C virus infections and by developments related to the corona pandemic. In view of the enormous interest from the academic world and the pharmaceutical industry, a variety of chemical and enzymatic synthesis routes have been developed since the first approval of an NA. The selective chemical synthesis of β-anomeric NAs through chemical N-glycosylation remains a challenging and, sometimes, a prohibitively expensive process, thus limiting the available chemical space. In response, full enzymatic cascades for the synthesis of NAs have been developed since the discovery of suitable biocatalysts. Despite significant success, particularly due to advances in enzyme engineering, constraints persist due to a limited substrate scope of the available biocatalysts. This mini-review aims to address both the challenges and potential of chemical and biocatalytic approaches in NA synthesis. It also illustrates how a combined strategy could substantially enhance synthesis efficiency as demonstrated by a few existing examples. Thus the authors hope to encourage scientists from both domains to join their efforts to drive innovative solutions in this field. |
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| ISSN: | 1878-1543 |