Browsing by Author "Lin, Shu-Yi"

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alpha-Glycosylation by D-Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin
(2012-05-30)
Zulueta, Medel Manuel L.
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Lin, Shu-Yi
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Lin, Ya-Ting
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Huang, Ching-Jui
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Wang, Chun-Chih
Numerous biomolecules possess alpha-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted beta-isomer. We report herein a versatile approach in affording full alpha-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.
In-situ Formation and Assembly of Gold Nanoparticles by Gum Arabic as Efficient Photothermal Agent for Killing Cancer Cells
(2013-10-01)
Liu, Ching-Ping
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Lin, Fong-Sian
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Chien, Chih-Te
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Tseng, Sheng-Yang
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Luo, Chih-Wei
Molecular design of near-infrared fluorescent Pdots for tumor targeting: aggregation-induced emission versus anti-aggregation-caused quenching
(2019-01-07)
Tsai, Wei-Kai
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Wang, Chun-I.
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Liao, Chia-Hsien
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Yao, Chun-Nien
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Kuo, Tsai-Jhen
Semiconducting polymer dots (Pdots) have recently emerged as a new type of ultrabright fluorescent probe that has been proved to be very useful for biomedical imaging. However, Pdots often suffer from serious fluorescence aggregation-caused quenching (ACQ) especially for near-infrared (NIR) fluorescent Pdots. This article compared two strategies to overcome the ACQ effect in near-infrared emissive Pdot systems: aggregation-induced emission (AIE) and anti-aggregation-caused quenching (anti-ACQ). The results show that the anti-ACQ platform outperforms the AIE system. The fluorescence quantum yield of anti-ACQ-based Pdots can be over 50% and the average per-particle brightness of the Pdots is about 5 times higher than that of the commercially available quantum dots. To help understand why the monomer conformations could greatly affect the optical properties of Pdots, molecular dynamics simulations were performed for the first time in such complicated Pdot systems. To demonstrate applications for in vivo fluorescence imaging, both microangiography imaging on living zebrafish embryos and specific tumor targeting on mice were performed. We anticipate that these studies will pave the way for the design of new highly fluorescent Pdot systems.
Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction
(2011-07-01)
Hu, Yu-Peng
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Lin, Shu-Yi
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Huang, Cheng-Yen
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Zulueta, Medel Manuel L.
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Liu, Jing-Yuan
Cell surface carbohydrates play significant roles in a number of biologically important processes. Heparan sulfate, for instance, is a ubiquitously distributed polysulfated polysaccharide that is involved, among other things, in the initial step of herpes simplex virus type 1 (HSV-1) infection. The virus interacts with cell-surface heparan sulfate to facilitate host-cell attachment and entry. 3-O-Sulfonated heparan sulfate has been found to function as an HSV-1 entry receptor. Achieving a complete understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences, the prepared 3-O-sulfonated sugars blocked viral infection in a dosage-dependent manner with remarkable similarity to one another.
Synthetic heparin and heparan sulfate oligosaccharides and their protein interactions
(2013-12-01)
Zulueta, Medel Manuel L.
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Lin, Shu-Yi
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Hu, Yu-Peng
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Hung, Shang-Cheng
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應用化學系
Heparin and heparan sulfate bind a host of basic proteins that take advantage of the sugar's dense structural information. The significance of these interactions in various aspects of development, physiology, and disease stimulated keen interest in evaluating structure-activity relationships. The well-defined heparin and heparan sulfate oligosaccharides needed for these studies can be mainly accessed by chemical synthesis and, more recently by chemoenzymatic means. The various synthetic strategies available to chemical synthesis have recently enabled the acquisition of several regular and irregular sequences, including a number of dodecasaccharides, through improved coupling methods and judicial protecting group manipulations. Controlled chain elongation and critical application of modification enzymes allowed the generation of well-defined constructs via chemoenzymatie synthesis. Investigations of various protein interactions with the synthetic constructs delivered valuable information that could aid future drug development endeavors.