Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA.
Departments of Biology, Bioengineering, & Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA.
Methods Mol Biol. 2022;2303:753-764. doi: 10.1007/978-1-0716-1398-6_56.
Glycosaminoglycan (GAG) side chains of proteoglycans are involved in a wide variety of developmental and pathophysiological functions. Similar to a gene knockout, the ability to inhibit GAG biosynthesis would allow us to examine the function of endogenous GAG chains. However, ubiquitously and irreversibly knocking out all GAG biosynthesis would cause multiple effects, making it difficult to attribute a specific biological role to a specific GAG structure in spatiotemporal manner. Reversible and selective inhibition of GAG biosynthesis would allow us to examine the importance of endogenous GAGs to specific cellular, tissue, or organ systems. In this chapter, we describe the chemical synthesis and biological evaluation of xyloside derivatives as selective inhibitors of heparan sulfate and chondroitin/dermatan sulfate proteoglycan biosynthesis.
糖胺聚糖 (GAG) 侧链的蛋白聚糖参与了广泛的发育和病理生理功能。类似于基因敲除，抑制 GAG 生物合成的能力将使我们能够检查内源性 GAG 链的功能。然而，普遍和不可逆地敲除所有 GAG 生物合成会导致多种影响，使得难以以时空方式将特定 GAG 结构的特定生物学作用归因于特定 GAG 结构。GAG 生物合成的可逆和选择性抑制将使我们能够检查内源性 GAG 对特定细胞、组织或器官系统的重要性。在本章中，我们描述了木糖苷衍生物作为肝素硫酸和软骨素/皮肤素硫酸蛋白聚糖生物合成的选择性抑制剂的化学合成和生物学评价。
