title: Synthesis of selective inhibitors of heparan sulfate and chondroitin sulfate proteoglycan biosynthesis.
abstract: 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.
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, Salt lake City, UT, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Mencio
authors.forename: Dinesh R
authors.initials: DR
authors.lastname: Garud
authors.forename: Balagurunathan
authors.initials: B
authors.lastname: Kuberan
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods*; D016466:CHO Cells; D011508:Chondroitin Sulfate Proteoglycans / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015203:Reproducibility of Results
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D006027:Glycosides; D006497:Heparan Sulfate; C010807:xylosides