Custom Nucleotide Sugar Synthesis

Natural and non-natural nucleotide sugars are of great interest in carbohydrate synthesis, which can be used as enzyme inhibitors or as tools for assay development and for the study of glycoconjugate biosynthesis. Enriched experience, profound expertise, and state-of-the-art instruments, Creative Biolabs offers top-quality service for nucleotide sugar synthesis. We are pleased to tailor the most appropriate strategies for nucleotide sugar synthesis to satisfy each demand of our clients.

Introduction of Nucleotide Sugar

Nucleotide sugars are the activated form of monosaccharides that serve as glycosyl donors for glycosyltransferases in the synthesis of cell wall polysaccharides. Structurally, nucleotide sugars are composed of a sugar or sugar derivative and a nucleoside mono- or diphosphate. They can be grouped into two classes, nucleoside diphosphate sugars (NDP-sugars) and nucleoside monophosphate sugars (NMP-sugars). In nature, there are numerous combinations of sugars and nucleotides. Although only nine different nucleotide sugars have so far been identified in mammalian cells, this number is much greater in other organisms. Most naturally occurring nucleotide sugars are NDP-sugars, such as common building blocks UDP-a-D-galactose and GDP-a-D-mannose, while biologically important representatives of NMP sugars are also present in nature, such as CMP-sialic acid and CMP-Kdo. Structural analogues of natural nucleotide sugars are potentially useful chemical tools for affinity chromatography, photoaffinity labeling, or as fluorophores for assay development.

Fig.1 General synthetic strategies for NDP-sugars and CMP-sugars. (Wagner, 2009)

General Strategies for Nucleotide Sugar Synthesis

Various methodologies have been developed to generate nucleotide sugars. 1) Chemical synthesis allows for the preparation of a diverse range of natural and unnatural structures. This method is challenging due to poor anomeric stereoselectivity, the need of multi-step procedures, and low yields. 2) Enzymatic methods can directly convert the free sugar into desired nucleotide sugar, without the need for protecting groups and afford the product with perfect regio- and stereo-selectivity. However, this method is less flexible due to the limited substrate specificity. 3) Combining chemical and enzymatic methods, a hybrid chemoenzymatic strategy has been successfully applied for the efficient synthesis of different sugar libraries. Using this strategy, glycan core precursors were first prepared via chemical synthesis and the precursors were subsequently extended to diverse and complex glycans via catalysis with robust glycosyltransferases. It is excited that this chemoenzymatic strategy has been used in the synthesis of UDP-α-6-N₃-glucose, showing efficient preparation of the desired product in large scale with relatively simple operation.

Custom Nucleotide Sugar Synthesis at Creative Biolabs

Nucleotide sugars serve as substrates for hundreds of glycosyltransferases in all organisms and they can be considered as direct precursors for synthesis of oligo- and polysaccharides, glycoproteins, glycolipids, sulfolipids, and glucosinolates, among other compounds. Efficient preparation of natural and non-natural nucleotide sugars is of considerable importance for synthetic, biological and medicinal chemistry.

Creative Biolabs employs chemical or chemoenzymatic method for the efficient synthesis of nucleotide sugars. Our strategies circumvent the traditional challenges of chemical synthesis by eliminating the need for protecting groups and advanced purification equipment. We have synthesized diverse nucleotide sugars with high quality, including but not limited to CMP-Neu5Az, UDP-GalNAcN₃, UDP-GalNAc6N₃, UDP-Gal6N₃, UDP-GalNAc, UDP-ManNAc and UDP-β-L-Arabinofuranose. Our methods can be scaled up to gram production reactions.

Highlights

• Synthesis of diverse types of nucleotide sugars
• Synthesis of nucleotide sugars derivatives
• Laboratory synthesis and rapid scale-up
• High flexibility and cost-effectiveness

Equipped with professional technical scientists and comprehensive powerful platform in glycan synthesis, Creative Biolabs is a perfect partner to offer our clients high-quality nucleotide sugars. For more detailed information, please feel free to contact us.

Reference

1. Wagner, G.K.; et al. A survey of chemical methods for sugar-nucleotide synthesis. Nat Prod Rep. 2009, 26(9):1172-94.

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