Mencio Caitlin, Garud Dinesh R, Kuberan Balagurunathan, Koketsu Mamoru
Interdepartmental Program in Neuroscience, University of Utah, Salt lake City, UT, USA.
Methods Mol Biol. 2015;1229:69-78. doi: 10.1007/978-1-4939-1714-3_8.
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 4-deoxy-4-fluoro-xylosides as selective inhibitors of heparan sulfate and chondroitin/dermatan sulfate proteoglycan biosynthesis.
蛋白聚糖的糖胺聚糖（GAG）侧链参与多种发育和病理生理功能。与基因敲除类似，抑制GAG生物合成的能力将使我们能够研究内源性GAG链的功能。然而，普遍且不可逆地敲除所有GAG生物合成会产生多种影响，使得难以在时空上赋予特定GAG结构特定的生物学作用。可逆且选择性地抑制GAG生物合成将使我们能够研究内源性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4-脱氧-4-氟木糖苷作为硫酸乙酰肝素和硫酸软骨素/硫酸皮肤素蛋白聚糖生物合成的选择性抑制剂的化学合成及生物学评价。
