Synthesis of N-Acetyllactosamine Sulfates and Analogues for Their Binding Specificity to Galectins
Date Issued
2009
Date
2009
Author(s)
Hsieh, Hsiao-Wu
Abstract
Galectins are a family of beta-galactoside-binding proteins that share significant sequence similarity in their carbohydrate-recognition domains (CRDs). So far fifteen galectins have been identified and categorized into three subgroups according to the type of CRDs. Accumulating evidence shows that galectins are related to numerous biological functions and corresponding diseases, such as immune responses, inflammation, cell apotosis, animal development and tumor progression. However, the function of galectins and the underlying mechanisms still remain unclear and need further investigations. In this thesis, a series of N-acetyllactosamine (LacNAc) sulfates and their analogues were synthesized. The critical reactions included protecting group manipulation, chemical glycosylation, and selective sulfation at a specific hydroxyl group. Different orthogonal protecting groups were introduced during the preparation of the building block synthesis to achieve the assembly of beta(1-3) or beta(1-4) glycosidic linkage, as well as selective sulfation at 3- or 6- position of Gal and 6-position of GlcNAc. Trichloroactaimidate and NIS/TfOH methods were studied for glycosylation with desired stereoselectivity and moderate yields. The final products were further studied for their binding specificity to galectins by AlphaScreenTM and immune assay. The preliminary results indicated that these compounds could impede B cell differentiation to antibody-secreting plasma cell, supporting the important role of galectin-glycan interaction.
Subjects
sulfation
N-acetyllactosamine
carbohydrate synthesis
galectins
B cell differentiation
Type
thesis
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