Tsai Ching-Ting, Zulueta Medel Manuel L, Hung Shang-Cheng
Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei 115, Taiwan; Department of Chemistry, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 106, Taiwan.
Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei 115, Taiwan; Institute of Chemistry, University of the Philippines, Diliman, Quezon City 1101, Philippines.
Curr Opin Chem Biol. 2017 Oct;40:152-159. doi: 10.1016/j.cbpa.2017.09.012. Epub 2017 Oct 13.
Heparin and heparan sulfate are glycosaminoglycans that modulate numerous biological processes. The desire to capture the structural diversity responsible for their functions provides notable issues during synthesis, including site-selective sulfonation, stereoselective glycosylation and the sheer number of probable targets at hand. With current advances in synthetic approaches, carbohydrate chemists generate these complex targets by chemical and enzymatic methods. Fondaparinux and a number of polysaccharides have been synthesized to probe anticoagulation and other biological functions. Moreover, a trove of structural information could be obtained by many analytical methods, which provide hints to the potential protein-binding sequences within the sugar chain. Further structure-activity relationship studies help unveil the secrets of the heparin/heparan sulfate code, providing potential candidates for drug development.
肝素和硫酸乙酰肝素是调节众多生物过程的糖胺聚糖。在合成过程中，要获取负责其功能的结构多样性存在显著问题，包括位点选择性磺化、立体选择性糖基化以及手头可能的靶点数量众多。随着合成方法的当前进展，碳水化合物化学家通过化学和酶促方法生成这些复杂的靶点。磺达肝癸钠和许多多糖已被合成以探究抗凝和其他生物学功能。此外，通过许多分析方法可以获得大量结构信息，这些方法为糖链内潜在的蛋白质结合序列提供了线索。进一步的构效关系研究有助于揭示肝素/硫酸乙酰肝素编码的秘密，为药物开发提供潜在候选物。
