Neuroactive chondroitin sulfate glycomimetics

Neuroactive chondroitin sulfate glycomimetics
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DOI:
10.1021/ja709993p
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发表时间:
2008-03-12
影响因子:
15
通讯作者:
Hsieh-Wilson, Linda C.
Hsieh-Wilson, Linda C.
中科院分区:
化学1区
文献类型:
--
作者:
Rawat, Manish;Gama, Cristal I.;Hsieh-Wilson, Linda C.

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我们报告了具有可调化学和生物学性质的硫酸软骨素(CS)糖模拟物的产生。我们的方法大大简化了复杂的糖胺聚糖的合成,提供了可编程硫酸化序列的合成可及的生物活性结构。使用这些glycopolymers,我们表明,多价相互作用是至关重要的调节CS活动,并发现一个意想不到的非自然的聚合物结构的宽容。我们设想,这些糖模拟物将有助于进一步探索大分子结构对糖胺聚糖功能的影响,并为在体内操纵CS活性提供有力的工具。
We report the generation of chondroitin sulfate (CS) glycomimetics with tunable chemical and biological properties. Our approach greatly simplifies the synthesis of complex glycosaminoglycans, providing synthetically accessible, bioactive structures of programmable sulfation sequence. Using these glycopolymers, we demonstrate that multivalent interactions are critical for modulating CS activity and discover an unexpected tolerance for unnatural polymeric architectures. We envision that these glycomimetics will facilitate further explorations into the influence of macromolecular structure on glycosaminoglycan function and provide powerful tools for manipulating CS activity in vivo.