Carbohydrates as the next frontier in pharmaceutical research

被引:160
作者
Werz, DB [1 ]
Seeberger, PH [1 ]
机构
[1] ETH Honggerberg, Swiss Fed Inst Technol, Organ Chem Lab, CH-8093 Zurich, Switzerland
关键词
automated synthesis; carbohydrates; glycobiology; glycoconjugates; heparin; microarrays;
D O I
10.1002/chem.200500025
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Synthetic carbohydrates and glycoconjugates are used to study their roles in biological important processes such as inflammation, cell-cell recognition, immunological response, metastasis, and fertilization. The development of an automated oligosaccharide synthesizer greatly accelerates the assembly of complex, naturally occurring carbohydrates as well as chemically modified oligosaccharide structures and promises to have major impact on the field of glycobiology. Tools such as microarrays, surface plasmon resonance spectroscopv, and fluorescent carbohydrate conjugates to map interactions of carbohydrates in biological systems are presented. Case studies of the successful application of carbohydrates as active agents are discussed, for example, fully synthetic oligosaccharide vaccines to combat tropical diseases (e.g., malaria), bacterial infections (e.g., tuberculosis), viral infections such as HIV, and cancer. Aminoglycosides serve as examples of drugs acting through carbohydrate-nucleic-acid interactions, while heparin works by carbohydrate-protein interactions. A general, modular strategy for the complete stereoselective synthesis of defined heparin oligosaccharides is presented. A carbohydrate-functionalized fluorescent polymer has been shown to detect miniscule amounts of bacteria faster than commonly used methods.
引用
收藏
页码:3194 / 3206
页数:13
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