Al-Horani Rami A, Karuturi Rajesh, Verespy Stephen, Desai Umesh R
Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 E. Leigh Street, Suite 212, Richmond, VA, 23219, USA.
Methods Mol Biol. 2015;1229:49-67. doi: 10.1007/978-1-4939-1714-3_7.
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.
在硫酸化糖胺聚糖（GAGs）几乎所有的生物活性情况中，硫酸基团对于与靶蛋白相互作用至关重要。一个日益流行的模式是，可以设计出合适的、硫酸化的、非糖类GAG模拟物，以模拟或干扰天然GAG序列的生物学功能，从而发现拮抗剂或激动剂。很多时候，这些硫酸化的非糖类GAG模拟物（NSGMs）可以根据母体GAG-蛋白质相互作用进行计算机设计。小的硫酸化NSGMs可能具有相当大的芳香性，以便在与靶蛋白相互作用时构建疏水、氢键、库仑力或阳离子-π力，从而相对于母体GAG具有更高的作用特异性。硫酸化NSGMs可以在基于微波的条件下通过化学硫酸化，从合适的天然多酚一步轻松合成。我们描述了对几种小的多酚支架进行基于微波的硫酸化的分步程序，以便以高产率制备每分子含有1至10多个硫酸基团的均匀NSGMs。
