Browsing by Author "Lin, Hsien-Ya"

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Dissecting the Structure-Activity Relationship of Galectin-Ligand Interactions
(2018-02-01)
Chan, Yi-Chen
;
Lin, Hsien-Ya
;
Tu, Zhijay
;
Kuo, Yen-Hsi
;
Hsu, Shang-Te Danny
Galectins are -galactoside-binding proteins. As carbohydrate-binding proteins, they participate in intracellular trafficking, cell adhesion, and cell-cell signaling. Accumulating evidence indicates that they play a pivotal role in numerous physiological and pathological activities, such as the regulation on cancer progression, inflammation, immune response, and bacterial and viral infections. Galectins have drawn much attention as targets for therapeutic interventions. Several molecules have been developed as galectin inhibitors. In particular, TD139, a thiodigalactoside derivative, is currently examined in clinical trials for the treatment of idiopathic pulmonary fibrosis. Herein, we provide an in-depth review on the development of galectin inhibitors, aiming at the dissection of the structure-activity relationship to demonstrate how inhibitors interact with galectin(s). We especially integrate the structural information established by X-ray crystallography with several biophysical methods to offer, not only in-depth understanding at the molecular level, but also insights to tackle the existing challenges.
Synthesis of Oligomeric Mannosides and Their Structure-Binding Relationship with Concanavalin A
(2014-07-01)
Li, Chen-Wei
;
Hon, Kai-Wei
;
Ghosh, Bhaswati
;
Li, Po-Han
;
Lin, Hsien-Ya
Small glycodendrimers with a-mannosyl ligands were synthesized by using copper-catalyzed azide-alkyne coupling chemistry and some of these molecules were used as multivalent ligands to study the induction of concanavalin A (Con A) precipitation. The results showed that the monovalent mannose ligand could induce the precipitation of Con A. This unexpected finding initiated a series of studies to characterize the molecular basis of the ligand-lectin interaction. The atypical precipitation is found to be specific to the mannose, fluorescein moiety (FITC), and Con A. Apparently the mannose ligand binds to Con A through hydrogen-bonding interactions, whereas the binding of FITC is mediated by hydrophobic forces.