Browsing by Author "Yeh, Che-Jui"

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Single-Step Per-O-Sulfonation of Sugar Oligomers with Concomitant 1,6-Anhydro Bridge Formation for Binding Fibroblast Growth Factors
(2019-01-18)
Yeh, Che-Jui
;
Ku, Chiao-Chu
;
Lin, Wei-Chen
;
Fan, Chiao-Yuan
;
Zulueta, Medel Manuel L.
Many circulating cancer-related proteins, such as fibroblast growth factors (FGFs), associate with glycosaminoglycans-particularly heparan sulfate-at the cell surface. Disaccharide analogues of heparan sulfate had previously been identified as the shortest components out of the sugars that bind to FGF-1 and FGF-2. Taking note of the typical pose of l-iduronic acid, we conceived of per-O-sulfonated analogues of such disaccharides, and devised a single-step procedure for per-O-sulfonation of unprotected sugars with concomitant 1,6-anhydro bridge formation to achieve such compounds through direct use of SO3Et3N as sulfonation reagent and dimethylformamide as solvent. The synthesized sugars based on the oligomaltose backbone bound FGF-1 and FGF-2 mostly at the sub-micromolar level, although the tetrasaccharide analogue achieved low-nanomolar binding with FGF-2.
Synthesis of hyaluronic acid oligosaccharides with a GlcNAc-GlcA repeating pattern and their binding affinity with CD44
(2020-07-28)
Yeh, Che-Jui
;
Zulueta, Medel Manuel L.
;
Li, Yaw-Kuen
;
Hung, Shang-Cheng
;
應用化學系
Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan in the extracellular matrix and a ligand of CD44, a transmembrane glycoprotein that is important in cell migration. Crystal and NMR studies found a hexasaccharide of the pattern (GlcA-GlcNAc)(3)as the shortest HA that could bind to CD44, but molecular dynamics simulations indicated that a tetrasaccharide of the pattern (GlcNAc-GlcA)(2)is the key structure interacting with CD44. Access to oligomers with such a repeat pattern is crucial in binding studies with CD44. Here we developed a synthetic procedure to afford the HA oligosaccharides with the GlcNAc-GlcA repeating unit and measured the binding interaction between these sugars and human CD44 by isothermal titration calorimetry (ITC). During the chemical synthesis, we successfully generated the beta-glycosidic bond in the absence of neighbouring group participation and overcome the issues in the oxidation step. In addition, ammonia-free dissolving metal reduction for debenzylation and azido reduction has been applied in carbohydrate synthesis for the first time. ITC analysis revealed that the HA tetrasaccharide (GlcNAc-GlcA)(2)could indeed interact and bind to the human CD44.