Custom Carbohydrate Antigen Synthesis
Having worked with carbohydrate antigens for many years, CD BioGlyco can customize its synthesis according to customers' research needs. We have confidence to be your essential research assistant in the field of glycobiology.
On the surface of cancer cells, abnormal glycosylation occurs, including glycan truncation, neo-glycan expression, and increase/decrease in glycan epitope density. A common aberration in adenocarcinoma is an over-simplification of mucins' glycosylation pattern. Mucins are highly glycosylated proteins and a key component of mucus and other biological lubricants. The tumor-associated carbohydrate antigen (TACA) is a family of oligosaccharides, a subclass of which is expressed on mucin glycopeptides in cancer. ACA can be divided into three categories: the mucin-based glycopeptides (Tn, sialyl-Tn, and TF), lactosamine series expressed as glycoproteins and glycolipids (sialyl Lewisx, Lewisx, sialyl LewisA, and LewisY), and truncated gangliosides (Globo-H, stage-specific embryonic antigen 3, and ganglioside monosialic 2).
The first category has attracted attention due to its relative simplicity and exclusivity to cancer. Although the second category may be used as vaccine targets, their structural complexity limits their use as synthetic vaccines. Gangliosides have shown great potential and may become a rich source of immunological targets in the future. For decades, compared with traditional therapies (chemotherapy and radiotherapy), cancer immunotherapy has great advantages, which has opened the way for the development of TACA molecular design, thereby promoting the development of specific therapies for cancer.
We deploy intricate synthetic tactics integrating multicomponent single-vessel assembly to forge elaborate oligosaccharide frameworks. This paradigm enables accelerated construction of convoluted glycan antigens, frequently exhibiting superior assembly fidelity versus incremental methodologies. Mastery over stereochemical governance—notoriously demanding in saccharide synthesis—guarantees rigorous α/β anomeric configuration. Our designs incorporate building blocks exhibiting orthogonally reactive handles, permitting donor-specific activation for regimented glycosylation.
Conjugating enzymatic precision with synthetic plasticity, our dual-strategy paradigm offers potent avenues to intricate epitopes. Such convergent tactics facilitate gram-scale, cost-efficient production of antigens like Neu5Gc from glucose precursors. This approach excels in delivering pristine antigens for in vitro and in vivo interrogation, circumventing heterogeneity constraints.
Our mastery of protective group chemistry is fundamental to navigating the multi-functional nature of carbohydrates. We strategically apply and remove protecting groups to ensure selective reactions and prevent undesired side products, optimizing the overall synthesis yield and purity.
CD BioGlyco has successfully developed several effective strategies to synthesize different types of carbohydrate antigens. The synthesized carbohydrate antigens are verified by nuclear magnetic resonance (NMR) and glycan microarray analysis. And for the shortcomings of low immunogenicity and low metabolic stability of synthetic antigens, we have developed different optimization strategies:
Based on the target structure, our scientists design a tailored synthesis strategy, selecting the most appropriate chemical and/or chemo-enzymatic methodologies. This involves careful planning of building blocks, protective group schemes, and reaction conditions to optimize efficiency and yield.
Individual monosaccharide building blocks and key disaccharide/oligosaccharide intermediates are synthesized and meticulously purified to ensure high-quality starting materials for the subsequent coupling steps.
The core of the synthesis involves the strategic coupling of saccharide units through glycosylation reactions. This iterative process builds the target carbohydrate antigen step-by-step, with careful monitoring and optimization at each stage to achieve the desired stereochemistry and yield.
Once the complete carbohydrate antigen backbone is formed, all temporary protective groups are selectively removed. The crude product then undergoes comprehensive purification using advanced chromatographic techniques to isolate the target molecule with high purity.
The purified carbohydrate antigen undergoes stringent quality control analysis using a suite of analytical tools to confirm its identity, purity, and structural integrity. A detailed certificate of analysis is provided, ensuring full transparency and confidence in the delivered product.
DOI.: 10.1021/acs.orglett.5c01560
Journal: Organic Letters
IF: 5.0
Published: 2025
Results: The authors developed a highly stereoselective, iron-catalyzed method for synthesizing biologically important Tn antigens (O-linked GalNAc-Ser/Thr glycopeptides) on a multigram scale. This novel glycal 1,2-cis-aminoglycosylation reaction uses an iron catalyst to enable exclusive α-selectivity across diverse galactosyl donors (e.g., 3,4-di-O-acetyl-6-O-TBS-D-galactal and tri-O-acetyl-D-galactal) and amino acid acceptors (Ser/Thr with various N-protecting groups), overcoming previous limitations in stereocontrol and substrate scope. The method was optimized to minimize side reactions and scaled efficiently (up to 20 mmol). Post-glycosylation transformations were streamlined using rapid deprotection sequences (e.g., HCl-mediated N-Boc removal, hydrogenolysis, methanolysis) to deliver single-diastereomer Tn antigens (1a/1b) and N-Fmoc-protected building blocks (16a/16b) in high yields, providing a practical route for glycobiology research and glycopeptide synthesis.
Our custom carbohydrate antigen synthesis technology empowers the creation of standardized, pathogen-specific antigens with critical fidelity, particularly for bacterial polysaccharides where glycan microheterogeneity dictates immunogenic potency. As a direct extension of this capability, we offer specialized production services for high-priority pathogens.
CD BioGlyco can customize different experimental programs to meet the different research needs of customs. The optimized methods we adopted can solve most of the shortcomings of synthetic carbohydrate antigens and provide the best quality products for customers' research.
Customers can contact our employees directly and we will respond promptly. If you are interested in our services, please contact us for more detailed information.
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