Structural highlights
Function
NTD_LACLE Catalyzes the cleavage of the glycosidic bond of 2'-deoxyribonucleosides and the transfer of the deoxyribosyl moiety to an acceptor purine or pyrimidine base.[1] [2]
Publication Abstract from PubMed
Nucleosides are pervasive building blocks that are found throughout nature and used extensively in medicinal chemistry and biotechnology. However, the preparation of base-modified analogues using conventional synthetic methodology poses challenges in scale-up and purification. In this work, an integrated approach involving structural analysis, screening and reaction optimization, is established to prepare 2'-deoxyribonucleoside analogues catalysed by the type II nucleoside 2'-deoxyribosyltransferase from Lactobacillus leichmannii (LlNDT-2). Structural analysis in combination with substrate profiling, identified the constraints on pyrimidine and purine acceptor bases by LlNDT2. A solvent screen identifies pure water as a suitable solvent for the preparation of high value purine and pyrimidine 2'-deoxyribonucleoside analogues on a gram scale under optimized reaction conditions. This approach provides the basis to establish a convergent, step-efficient chemoenzymatic platform for the preparation of high value 2'-deoxyribonucleosides.
Gram-scale enzymatic synthesis of 2'-deoxyribonucleoside analogues using nucleoside transglycosylase-2.,Salihovic A, Ascham A, Taladriz-Sender A, Bryson S, Withers JM, McKean IJW, Hoskisson PA, Grogan G, Burley GA Chem Sci. 2024 Aug 27;15(37):15399-407. doi: 10.1039/d4sc04938a. PMID:39234214[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Porter DJ, Merrill BM, Short SA. Identification of the active site nucleophile in nucleoside 2-deoxyribosyltransferase as glutamic acid 98. J Biol Chem. 1995 Jun 30;270(26):15551-6. PMID:7797550
- ↑ Armstrong SR, Cook WJ, Short SA, Ealick SE. Crystal structures of nucleoside 2-deoxyribosyltransferase in native and ligand-bound forms reveal architecture of the active site. Structure. 1996 Jan 15;4(1):97-107. PMID:8805514
- ↑ Salihovic A, Ascham A, Taladriz-Sender A, Bryson S, Withers JM, McKean IJW, Hoskisson PA, Grogan G, Burley GA. Gram-scale enzymatic synthesis of 2'-deoxyribonucleoside analogues using nucleoside transglycosylase-2. Chem Sci. 2024 Aug 27;15(37):15399-407. PMID:39234214 doi:10.1039/d4sc04938a
