The Lea antigen, including its sialylated form sLea, is a blood group antigen existing in glycolipids and glycoproteins on cell surfaces, including erythrocytes and various normal cells. While sLea is naturally present in specific normal tissues such as fibroblasts and epithelial cells, it is significantly elevated in several cancer types marked by increased fucosylation. These cancers encompass colon, pancreatic, gallbladder/bile duct, breast, cholangiocarcinoma, and small-cell lung cancer. Recognized as CA19-9, sLea is an early tumor-associated carbohydrate antigen (TACA) and serves as a valuable serum biomarker for prognosis, postoperative monitoring, and assessing therapeutic responses in pancreatic and gastrointestinal cancers.
The intricate structural complexity of Lewis blood group antigens has intrigued numerous synthetic carbohydrate researchers. The sulfoxide glycosylation method offers a uniform set of reaction conditions that enable the stereo-selective formation of all glycosidic linkages within the Lewis blood group antigens Lea, Leb, and Lex, as illustrated in Fig.1. A gram-scale synthesis of Lea antigens (LeaProN3) and a library of sialyl Lea antigens (sLeaProN3) including various sialic acid forms may also be produced using a chemoenzymatic technique (Fig.2).
Fig.1 The synthesis of Lea began with the coupling of phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-R-D-glucopyranoside with the per-pivaloyl galactosyl sulfoxide. (Yan & Kahne, 1996)
Fig.2 The chemoenzymatic approach for the gram-scale synthesis of Lea. (Tasnima, et al., 2019)
By combining existing synthetic routes and literature support, our company can customize synthetic routes for different product sizes, purities, and application scenarios. Here is a standard of our company's process of customized solutions for production services. Relying on our advanced experimental platform and excellent experimental staff, as well as the support of our chemists, we are confident that we can be the right hand of our clients in the field of sugar chemistry, providing our support. Besides, we also provide other Tumor-Associated Lacto-series Antigen Production Services such as SLea Antigen and Leb Antigen, and we expect to work for clients in the field of Tumor-Associated Carbohydrate Vaccine Development.
Fig.3 The standard scheme for the synthesis of Lea antigen. (CD BioGlyco)
Elevated Lea antigen levels in blood serve as an indicator of cancer presence, aiding early diagnosis. It plays a pivotal role in determining prognosis, postoperative monitoring, and assessing therapeutic responses. Monitoring Lea antigen levels during cancer treatment provides valuable insights. Additionally, Lea antigen contributes to research on aberrant glycosylation patterns in cancer cells, shedding light on cancer biology and potential targeted therapies.
Technology: Chemoenzymatic synthesis, glycosyltransferase, Lewis a, sialyl Lewis a, sialic acid, protecting group-free glycosylation
Journal: Carbohydrate Research
IF: 3.1
Published: 2019
Results: The synthesis of Lea trisaccharide as a potential acceptor substrate for sialyltransferase-catalyzed sialylation reactions, aimed at producing desired sLea tetra-saccharides with various sialic acid forms, was undertaken. The glycoside GlcNAcProN3 was produced chemically, with a protecting group-free glycosylation process employing N'-glycosyl p-toluenesulfonohydrazides (GSHs) as glycosyl donors, as proposed by Gudmundsdottir and Nitz, emerging as an excellent choice. This approach demonstrated remarkable efficiency, especially when applied to 2-acetamido-sugars like free N-acetylglucosamine (GlcNAc) and unshielded disaccharides that possess free GlcNAc at the reducing end. The reactions yielded favorable results with high efficiency and β-selectivity.
Fig.4 Gram-scale chemoenzymatic synthesis of LeaβProN3. (Tasnima, et al., 2019)
CD BioGlyco has established a well-equipment lab to provide our clients with strong support for Lea antigen production and professional custom services. If you would like to know more about our service, please do not hesitate to contact us.
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