Gandhi Neha S, Mancera Ricardo L
Western Australian Biomedical Research Institute, Curtin University of Technology, Perth, WA 6845, Australia.
Chem Biol Drug Des. 2008 Dec;72(6):455-82. doi: 10.1111/j.1747-0285.2008.00741.x.
Glycosaminoglycans (GAGs) are important complex carbohydrates that participate in many biological processes through the regulation of their various protein partners. Biochemical, structural biology and molecular modelling approaches have assisted in understanding the molecular basis of such interactions, creating an opportunity to capitalize on the large structural diversity of GAGs in the discovery of new drugs. The complexity of GAG-protein interactions is in part due to the conformational flexibility and underlying sulphation patterns of GAGs, the role of metal ions and the effect of pH on the affinity of binding. Current understanding of the structure of GAGs and their interactions with proteins is here reviewed: the basic structures and functions of GAGs and their proteoglycans, their clinical significance, the three-dimensional features of GAGs, their interactions with proteins and the molecular modelling of heparin binding sites and GAG-protein interactions. This review focuses on some key aspects of GAG structure-function relationships using classical examples that illustrate the specificity of GAG-protein interactions, such as growth factors, anti-thrombin, cytokines and cell adhesion molecules. New approaches to the development of GAG mimetics as possible new glycotherapeutics are also briefly covered.
糖胺聚糖（GAGs）是重要的复合碳水化合物，通过调节其各种蛋白质伴侣参与许多生物过程。生物化学、结构生物学和分子建模方法有助于理解此类相互作用的分子基础，为利用GAGs的巨大结构多样性发现新药创造了机会。GAG-蛋白质相互作用的复杂性部分归因于GAGs的构象灵活性和潜在的硫酸化模式、金属离子的作用以及pH对结合亲和力的影响。本文综述了目前对GAGs结构及其与蛋白质相互作用的理解：GAGs及其蛋白聚糖的基本结构和功能、它们的临床意义、GAGs的三维特征、它们与蛋白质的相互作用以及肝素结合位点和GAG-蛋白质相互作用的分子建模。本综述使用经典例子，如生长因子、抗凝血酶、细胞因子和细胞粘附分子，重点介绍了GAG结构-功能关系的一些关键方面，这些例子说明了GAG-蛋白质相互作用的特异性。还简要介绍了开发GAG模拟物作为可能的新型糖疗法的新方法。
