α-Glycosylation by d -Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin
| Autor: | Ya-Ting Lin, Zhonghao Shi, Medel Manuel L. Zulueta, Tsung-I Tsai, Shang-Cheng Hung, Chun-Chih Wang, Deli Irene, Chi-Huey Wong, Shu-Yi Lin, Yu-Peng Hu, Chiao-Chu Ku, Chia-Lin Chyan, Liang-Hin Lim, Susan D. Arco, Ching-Jui Huang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Glycosylation
Stereochemistry Disaccharides Biochemistry Catalysis Substrate Specificity chemistry.chemical_compound Colloid and Surface Chemistry Lectins medicine Protecting group Glucosamine Heparin Chemistry Leaving group Stereoisomerism Mycobacterium tuberculosis General Chemistry Heparan sulfate Hemagglutinin HEXA Peptide Fragments Stereoselectivity medicine.drug |
| Zdroj: | Journal of the American Chemical Society. 134:8988-8995 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja302640p |
| Popis: | Numerous biomolecules possess α-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted β-isomer. We report herein a versatile approach in affording full α-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|