Custom Sugar-Nucleotide Synthesis
Overview
Sugar-nucleotide is of great significance in mediating biological processes and the development of carbohydrate drugs. CD BioGlyco has many years of experience in sugar-nucleotide synthesis and can customize high-quality synthesis services according to customers' research needs. We have the confidence to be your essential research assistant in the field of glycobiology.
Key Technologies
Based on our expertise at CD BioGlyco, the key technologies enabling our custom sugar-nucleotide synthesis are:
- Chemical synthesis: For diverse natural and unnatural structures.
- Enzymatic synthesis: Leveraginag glycosyltransferases for high regio- and stereospecificity.
- Chemoenzymatic synthesis: Combining chemical precursor synthesis with enzymatic elaboration.
- One-pot multienzyme (OPME) Synthesis: Efficiently producing NDP-sugars and NMP-sugars.
- Customized route design & optimization: Overcoming sulubility, stability (pyrophosphate/glycosidic bonds), and purification challenges, including counter-ion selection. We master these complex methods to deliver high-quality sugar-nucleotides.
Structurally, a sugar-nucleotide is composed of a sugar or sugar derivative and a nucleoside monophosphate or diphosphate. Sugar-nucleotide is a necessary intermediate for carbohydrate metabolism and glycoconjugate biosynthesis. The biosynthesis of glycans and glycoconjugates depends on the activation of monosaccharides as sugar nucleotides. They are composed of an activated sugar donor that is glycosylated onto a diverse range of acceptors, typified by glycosyltransferase-catalyzed processes for the assembly of glycosides and oligo- or polysaccharides.
Sugar-nucleotides and structural analogs can be used as substrates for enzymatic reactions in carbohydrate synthesis, as powerful tools for studying glycoconjugate biosynthesis, and they have the potential as enzyme inhibitors in new therapeutic strategies. Besides, they are also important for the provision of structurally defined homogenous analytical standards.
Therefore, the effective preparation of natural and unnatural sugar-nucleotide is of great significance in both synthetic biology and medicinal chemistry. The synthesis of sugar-nucleotides is more difficult because of many factors: Sugar-nucleotides synthesis can be difficult due to many factors: the low solubility of sugar nucleotides in organic solvents, the presence of polar or charged functional groups, as well as the sensitivity of glycosidic and pyrophosphate bonds to hydrolytic cleavage.
Custom Sugar-Nucleotides Synthesis at CD BioGlyco
CD BioGlyco provides a variety of professional sugar-nucleotide synthesis services. Clients have several options to choose what service suits their research plan the most. Besides the custom sugar-nucleotides synthesis services we offer, CD BioGlyco also provides other Custom Carbohydrate Synthesis Services on our Glyco™ Synthesis Platform.
- Chemical synthesis can prepare various natural and unnatural structures. This method has multiple steps and is challenging.
- Enzymatic synthesis has the characteristics of high location specificity and stereospecificity. It simulates the synthesis steps of sugar chains in organisms and is an effective alternative to organic chemical synthesis.
- Combining chemical and enzymatic methods. Firstly, the core precursor is prepared by chemical synthesis, and then the precursor is expanded into a variety of complex glycans by glycosyltransferase catalysis.
CD BioGlyco also offers specialized services for One-pot Multienzyme (OPME)-based NDP-sugar Synthesis and One-pot Multienzyme (OPME)-based NMP-sugar Synthesis. These services enable the efficient synthesis of NDP-sugars and NMP-sugars, which are crucial intermediates in glycosylation processes.
Nucleoside&Nucleotide Synthesis Service
Within our dedicated synthesis core, we architect nucleoside and nucleotide entities through integrated chemical, enzymatic, and biocatalytic platforms. My team leverages this trifurcated proficiency to furnish clients with rigorously characterized, application-specific molecules spanning biomedical research to therapeutic development.
For nucleosides, we deploy three complementary routes:
Nucleoside Chemical Synthesis enables atomically precise scaffolds featuring non-natural modifications via stereocontrolled glycosylation.
Nucleoside Enzymatic Synthesis
Nucleoside Enzymatic Synthesis exploits transglycosylases and kinases for chiral purity on multi-gram scales.
Nucleoside Cell Factory Synthesis
While our Nucleoside Cell Factory Synthesis harnesses engineered microbial systems for complex, metabolically derived analogs.
Each methodology undergoes stringent optimization—selectivity, titer, and isolation protocols are calibrated per compound complexity.
- Nucleotide access routes are equally specialized:
Nucleotide Chemical Synthesis achieves phosphoramidite or pyrophosphate ligations under anhydrous catalysis, ideal for isotopically labeled or backbone-modified species.
Nucleotide Microbial Synthesis
Nucleotide Microbial Synthesis employs high-density fermentation of recombinant strains for economical triphosphate production.
Nucleotide Enzymatic Digestion
Nucleotide Enzymatic Digestion streamlines nucleotide pool fractionation from biological matrices via immobilized phosphatase/nuclease columns.
Custom Oligonucleotide Synthesis Service
We orchestrate the design, synthesis, and refinement of oligonucleotides with atomic-level precision across chemical, enzymatic, and chromatographic regimes.
Solid-phase Chemical Synthesis
Solid-phase chemical synthesis executes rapid phosphoramidite couplings on controlled-pore glass (CPG) or polystyrene beads, enabling automated synthesis with site-specific phosphorothioate.
Liquid-phase Chemical Synthesis
Liquid-phase chemical synthesis supports large-scale (gram-level) production of oligonucleotides unstable on solid supports or requiring unique solution-phase cyclization.
Our enzymatic synthesis method employs T7 RNA polymerase or terminal deoxynucleotidyl transferase (TdT) for unnatural base-incorporated templates or nuclease-resistant thiophosphate backbones—ideal for mRNA payloads and aptamer evolution.
Post-synthesis, our oligonucleotide fragment purification service resolves critical impurity profiles:
Polynucleotide Synthesis Service
In DNA synthesis, we deploy three synergistic paths:
Chemical DNA Synthesis leverages automated phosphoramidite chemistry for rapid assembly of modified strands featuring phosphorothioates, bridged nucleic acids (BNAs), or bioconjugates.
Enzymatic DNA Synthesis utilizes terminal TdT or template-independent polymerases for scarless long-fragment assembly.
Hybrid DNA Synthesis interweaves enzymatic elongation with chemical segment ligation for cost-efficient megabase-scale constructs.
We offer comprehensive RNA synthesis services, where we leverage our expertise in nucleic acid chemistry and molecular biology to create high-quality RNA oligonucleotides tailored precisely to your research needs. Whether you require standard RNA, modified RNA with specific chemical groups, or even large-scale quantities for therapeutic applications, we handle every step from design to purification. Our commitment is to provide you with reliable, custom-synthesized RNA that meets the stringent demands of your experiments, empowering your breakthroughs in gene expression studies, RNA interference, drug discovery, and beyond.
Post-synthesis, our purification service eliminates truncations, misfolds, and endotoxins through orthogonal methods:
Nucleoside&Nucleotide Modification Service
We engineer precision-modified nucleosides and nucleotides through tailored chemical and enzymatic strategies, enabling bespoke functionalities for therapeutic discovery, diagnostic probes, and mechanistic studies. Our platform integrates six specialized modification pathways to address diverse biomedical challenges.
We engineer targeted chemical alterations to nucleobases (purines/pyrimidines) to enhance stability, functionality, or detection capabilities of nucleic acids. Key subservices include:
We engineer precision alterations to sugar moieties in nucleosides, nucleotides, and glycans to enhance stability, functionality, and targeting for therapeutics, diagnostics, and structural studies. Our platform integrates seven specialized pathways:
We specialize in the strategic redesign of nucleotide phosphate groups to overcome biological instability and enhance therapeutic performance through four core techniques.
Phosphate Group Production by Polar Group Service
Transforming polar moieties (e.g., hydroxyl, carboxyl) into bioactive phosphates/phosphonates, increasing hydrophilicity for enzyme targeting and metal chelation diagnostics.
Phosphate Group Replacement of P-O Bond by P-N Bond Service
Surgically replacing P-O bonds with phosphoramidate links (P-N), achieving nuclease resistance critical for in vivo siRNA persistence.
Mono-, Di-, and Tri-phosphate Modification Service
Constructing mono/di/tri-phosphate variants, including hydrolytically stable analogs (e.g., α,β-methylene ATP) for prodrug metabolism control.
Phosphoramide-based Nucleotide Modification Service
Installing phosphorodiamidate morpholinos (PMOs) or stereodefined phosphoramidates for RNase H-independent gene silencing.
Fluorescent labeling modification service incorporates Cy3/Cy5, FITC, or TAMRA at nucleobase, sugar, or phosphate positions for real-time tracking.
We introduce 13C/15N isotopes into bases, sugars, or phosphates for NMR-based metabolic flux analysis or quantitative MS proteomics, supporting drug ADME profiling and nucleotide turnover studies.
Radionuclide labeling modification conjugates 32P, 99mTc, or 125I for in vivo biodistribution imaging research or targeted radiotherapeutic studies.
Oligonucleotide Modification Service
We engineer precision-modified oligonucleotides to enhance their stability, targeting, and functionality for advanced therapeutic and diagnostic research applications. Our platform leverages six core modification strategies—each tailored to overcome biological barriers and optimize performance.
We install terminal 5'/3'-monophosphates or cyclic phosphates via enzymatic (kinases) or chemical (phosphoramidite) methods to prime molecules for ligation, labeling, or cellular uptake studies.
Replace non-bridging oxygen with sulfur in phosphodiester bonds, conferring nuclease resistance and improved pharmacokinetics vital for in vivo antisense therapeutics.
2'-positions are modified, or LNAs and BNAs are deployed, to enhance duplex stability and melting temperature.
We engineer targeted alterations to nucleobases within oligonucleotides to enhance binding affinity, stability, and functionality for advanced therapeutics and diagnostics. Our platform integrates five specialized modification pathways—each optimized to address biological challenges while preserving sequence specificity:
- Oligonucleotide-based Affinity-plus Base Modification Service
- Oligonucleotide-based Inosine Modification Service
- Oligonucleotide-based 2'-O-methoxy-ethyl Bases (2'-MOE) Modification Service
- Oligonucleotide-based 2'-O-Methyl RNA Bases Modification Service
- Oligonucleotide-based Fluoro Bases Modification Service
At the heart of our innovation, we engineer precision linkers to transform oligonucleotides into multifunctional tools for targeted therapies, diagnostics, and nanotechnology. By integrating site-specific functional groups, we enable seamless conjugation, programmable assembly, and enhanced biodistribution.
- Amino-based Oligonucleotide Modification Service
- Biotin-based Oligonucleotide Modification Service
- Thiol-based Oligonucleotide Modification Service
- Alkyne-based Oligonucleotide Modification Service
- Azide-based Oligonucleotide Modification Service
- Adenylation-based Oligonucleotide Modification Service
- Digoxigenin-based Oligonucleotide Modification Service
We transform oligonucleotides into high-fidelity optical tools through site-specific fluorophore integration, enabling real-time molecular interrogation across therapeutics and diagnostics. Our tailored conjugation strategies ensure optimal brightness, stability, and multiplex compatibility while preserving oligo functionality.
Nucleoside-based Production Service
We provide the custom synthesis of all five primary nitrogenous bases—Adenine, Guanine, Cytosine, Thymine, and Uracil—as well as their modified or rare counterparts. Leveraging advanced synthetic techniques, we ensure that these fundamental building blocks of nucleic acids are produced with exceptional purity, ready for incorporation into your custom nucleoside or nucleotide synthesis or for direct use in various biochemical assays.
Our capabilities extend to the precise synthesis of ribonucleosides, which are crucial for RNA synthesis, enzymatic studies, and diagnostic applications. This includes the production of adenosine, guanosine, cytidine, and uridine, alongside their modified forms. Whether you require specific glycosidic linkages or unique modifications on the ribose sugar, we deliver custom ribonucleosides tailored to your exact specifications.
Nucleoside-based Adenosine Production Service
Nucleoside-based Cytidine Production Service
Nucleoside-based Guanosine Production Service
Nucleoside-based Uridine Production Service
Nucleoside-based 5-Methyluridine Production Service
For DNA-related research and applications, we offer the custom synthesis of deoxyribonucleosides, encompassing Deoxyadenosine, Deoxyguanosine, Thymidine, Deoxyuridine, and Deoxycytidine. Our process ensures the accurate formation of the deoxyribose-base bond and the integrity of the deoxyribose sugar, providing you with high-quality building blocks essential for oligonucleotide synthesis, PCR, sequencing, and other molecular biology techniques.
At our specialized facility, we provide comprehensive nucleoside-based derivative production services that encompass the precise chemical synthesis and modification of a wide array of nucleoside scaffolds, including Deoxyadenosine, Deoxycytidine, Deoxyguanosine, Deoxythymidine, Deoxyuridine, Dideoxynucleotide, Adenosine, Adenine, Cytosine, Cytidine, Guanosine, Guanine, Uridine, Uracil, Thymine, Ribothymidine, and Derivatives Featuring Diverse Backbone Sugars. Leveraging advanced synthetic methodologies such as de novo synthesis and selective functionalization—inspired by cutting-edge approaches in nucleoside analog development—we engineer these compounds with tailored modifications to meet specific research.
Nucleotide-based Production Service
At our specialized biotechnology facility, we deliver comprehensive nucleotide-based production services, encompassing a full spectrum of high-purity nucleotide synthesis and customization solutions. Our capabilities include:
One-pot Multienzyme (OPME)-based NDP-sugar Synthesis Service
We provide a specialized OPME-based NDP-sugar synthesis service, utilizing engineered enzyme cascades in a single reaction vessel to efficiently produce high-purity natural and modified nucleotide-activated sugars (e.g., UDP-glucose, GDP-mannose, and custom analogs). This integrated approach eliminates intermediate purification, enhances yields and reduces costs through in situ cofactor regeneration, enabling scalable synthesis from research to gram-scale production. Our rigorously validated platform delivers highly pure substrates critical for glycotherapeutic development, metabolic probing, and antiviral research, accelerating glycoscience innovation while bridging discovery and clinical translation.
One-pot Multienzyme (OPME)-based NMP-sugar Synthesis Service
We offer an OPME-based NMP-sugar synthesis service that provides an efficient and streamlined approach to synthesizing NMP sugars. This innovative service leverages the power of multiple enzymes working in concert within a single reaction vessel. Our OPME strategy eliminates the need for isolating intermediates, significantly reducing reaction time, costs, and waste generation. By carefully selecting and optimizing the enzymatic cascade, we can achieve high yields and purity of various NMP-sugars, which are crucial precursors for glycosylation reactions and the biosynthesis of complex glycans.
Publication Data
DOI.: 10.3390/molecules25235755
Journal: Molecules
IF: 4.6
Published: 2020
Results: This review comprehensively examines nucleotide sugars, focusing on their essential roles as glycosyl and phosphoglycosyl donors in the biosynthesis of carbohydrates and glycoconjugates across all living organisms. The author discusses the structures and diverse biosynthetic pathways of nucleotide sugars found in mammalian, plant, and bacterial cells, highlighting the structural variety, particularly in bacteria. A significant portion details the mechanisms of enzymatic reactions involving nucleotide sugars, including catalysis by glycosyltransferases (both retaining and inverting mechanisms), polyisoprenol-phosphate glycosyltransferases, phosphoglycosyl transferases (different superfamily mechanisms), and enzymes forming phosphodiester-linked carbohydrates. The review also covers the chemical reactivity and decomposition pathways of nucleotide sugars under different conditions (acidic, alkaline, metal-catalyzed), explaining why they are not typically used as chemical glycosyl donors. Finally, it summarizes both chemical and enzymatic (including efficient chemoenzymatic cascades) methods for synthesizing natural and modified nucleotide sugars, emphasizing their importance as tools for oligosaccharide synthesis, drug development (as enzyme inhibitors and therapeutic targets, especially against bacterial processes), and diagnostics. Overall, the review bridges biological and chemical perspectives on nucleotide sugars, emphasizing their fundamental importance and the methodologies to study and utilize them.
Workflow
Advantages
- Our hybrid approach combines chemical synthesis with engineered enzymes (kinases, pyrophosphorylases), accelerating the production of rare or unnatural nucleotides.
- We engineer structurally diverse analogs (e.g., fluorinated, azido-, or isotope-labeled sugars) with atomic-level control, enabling targeted interrogation of glycosylation pathways.
- Our expertise allows us to overcome complex synthetic challenges by strategically leveraging automated purification and AI-assisted route optimization.
Applications
- Unnatural sugar-nucleotides expand the substrate scope of glycosyltransferases, enabling the synthesis of non-natural glycoconjugates.
- Transition-state mimics or dead-end analogs inhibit bacterial cell wall biosynthesis enzymes (e.g., MurG, WecA) or cancer-associated glycosyltransferases.
- Synthetic sugar-nucleotides enable enzymatic printing of unnatural glycans onto microarrays for high-throughput screening of glycan-protein interactions (e.g., pathogen adhesion studies).
Associated Services
Through our advanced capabilities in custom sugar-nucleotide synthesis, we not only provide precision-engineered molecular tools for glycobiology research but also directly empower downstream therapeutic discovery, specifically enabling targeted inhibitor development against dysregulated glycosylation pathways. This seamless integration allows us to support strategic initiatives such as UDP-GlcA Inhibitor Development, GDP-Fuc Inhibitor Development, and CMP-Sia Inhibitor Development, where synthetic access to modified substrates and transition-state analogs unlocks new opportunities to intercept pathologic glycan signaling.
Frequently Asked Questions
CD BioGlyco customizes different experimental programs to meet the different research needs of customers. We have first-class experimental equipment and experienced researchers to provide you with professional sugar-nucleotide synthesis services. Customers can contact our employees directly and we will respond promptly. If you are interested in our services, please feel free to contact us for more detailed information.
Reference
- Mikkola, S. Nucleotide sugars in chemistry and biology. Molecules. 2020, 25(23): 5755. (Open Access)
Quick Links
Resources
- Oligonucleotide Modification Service
- Nucleoside-based Production Service
- Nucleotide-based Production Service
- Nucleoside & Nucleotide Synthesis Service
- Custom Oligonucleotide Synthesis Service
- Polynucleotide Synthesis Service
- Nucleoside & Nucleotide Modification Service
- One-pot Multienzyme (OPME)-based NDP-sugar Synthesis Service
- One-pot Multienzyme (OPME)-based NMP-sugar Synthesis Service