Synthesis of Glycosaminoglycan Mimetics Through Sulfation of Polyphenols
Synthesis of Glycosaminoglycan Mimetics Through Sulfation of Polyphenols
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DOI：
10.1007/978-1-4939-1714-3_7
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发表时间：
2015-01-01
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影响因子：
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通讯作者：
Desai, Umesh R.
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文献类型：
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作者：
Al-Horani, Rami A.;Karuturi, Rajesh;Desai, Umesh R.
在硫酸化糖胺聚糖生物活性的几乎所有情况下，硫酸根基团对于与靶蛋白相互作用至关重要。一个不断发展的范例是，可以设计适当的小的、硫酸化的、非糖GAG模拟物来模拟或干扰天然GAG序列的生物学功能，从而发现拮抗剂或激动剂。这些硫酸化NSGM可以基于亲本GAG-蛋白质相互作用进行多次计算设计。小的硫酸化NSGM可以具有相当大的芳香族特性，以便在它们与靶蛋白的相互作用中工程化疏水力、氢键力、库仑力或阳离子-π力，导致相对于亲本GAG的更高的作用特异性。硫酸化的NSGMs可以很容易地在微波条件下通过化学硫酸化从合适的天然多酚一步合成。我们描述了一步一步的程序来执行微波为基础的硫酸化的几个小的多酚支架，以制备均匀的NSGMs含有一个到10个以上的硫酸基团，每分子的高产率。
In nearly all cases of biological activity of sulfated GAGs, the sulfate group(s) are critical for interacting with target proteins. A growing paradigm is that appropriate small, sulfated, nonsaccharide GAG mimetics can be designed to either mimic or interfere with the biological functions of natural GAG sequences resulting in the discovery of either antagonist or agonist agents. A number of times these sulfated NSGMs can be computationally designed based on the parent GAG-protein interaction. The small sulfated NSGMs may possess considerable aromatic character so as to engineer hydrophobic, hydrogen-bonding, Coulombic or cation-pi forces in their interactions with target protein(s) resulting in higher specificity of action relative to parent GAGs. The sulfated NSGMs can be easily synthesized in one step from appropriate natural polyphenols through chemical sulfation under microwave-based conditions. We describe step-by-step procedures to perform microwave-based sulfation of several small polyphenol scaffolds so as to prepare homogenous NSGMs containing one to more than 10 sulfate groups per molecule in high yields.