Glycosaminoglycans (GAGs) are a heterogeneous family of unbranched polysaccharides that exist in either a free state or attached to proteins and are found on the cell surface as well as in the extracellular matrix. GAGs play essential roles in cellular and tissue homeostasis, and their metabolism is altered in response to several pathological conditions. Despite strong experimental evidence supporting the function of GAGs in various diseases, little is known about the regulation of GAG biosynthesis via pharmacological intervention. In recent studies, the effects of several experimental drugs on GAG biosynthesis in animal models of disease were examined and key enzymes involved in GAG biosynthesis were found to be druggable. In addition to experimental small‐molecule drugs that alter GAG biosynthesis, a number of clinically approved drugs modulate GAG metabolism, contributing to the therapeutic benefits associated with the use of these drugs. In this review article, we propose a classification scheme for drugs affecting GAG biosynthesis. Our goal is to present a rational approach to investigate the pharmacological regulation of these important biological molecules.

中文翻译：

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药物介导的糖胺聚糖生物合成调控

糖胺聚糖（GAGs）是非支链多糖的异质家族，其以游离态存在或以附着于蛋白质的形式存在于细胞表面以及细胞外基质中。GAG在细胞和组织动态平衡中起着至关重要的作用，它们的新陈代谢会根据几种病理状况而改变。尽管有强有力的实验证据支持GAG在各种疾病中的功能，但对通过药理学干预调节GAG生物合成的了解却很少。在最近的研究中，研究了几种实验药物对疾病动物模型中GAG生物合成的影响，并发现参与GAG生物合成的关键酶是可药用的。除了可以改变GAG生物合成的实验性小分子药物之外，许多临床批准的药物可调节GAG代谢，从而有助于与这些药物的使用相关的治疗益处。在这篇综述文章中，我们提出了影响GAG生物合成的药物分类方案。我们的目标是提出一种合理的方法来研究这些重要生物分子的药理学调控。