Xyloside Derivatives as Molecular Tools to Selectively Inhibit Heparan Sulfate and Chondroitin Sulfate Proteoglycan Biosynthesis

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Glycosaminoglycans

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2303))

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 xyloside derivatives as selective inhibitors of heparan sulfate and chondroitin/dermatan sulfate proteoglycan biosynthesis.

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References

  1. Götting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K (2000) Molecular cloning and expression of human UDP-D-xylose:proteoglycan core protein β-D-xylosyltranferase and its first isoform XT-II. J Mol Biol 304:517–528

    Article  Google Scholar 

  2. Lindahl U, Roden L (1966) The chondroitin 4-sulfate protein linkage. J Biol Chem 241:2113–2119

    Article  CAS  Google Scholar 

  3. Muir H (1958) The nature of the link between protein and carbohydrate of a chondroitin sulphate complex from hyaline cartilage. Biochem J 69:195–204

    Article  CAS  Google Scholar 

  4. Mikami T, Kitagawa H (2013) Biosynthesis and function of chondroitin sulfate. Biochim Biophys Acta 1830:4719–4733

    Article  CAS  Google Scholar 

  5. Lin X (2004) Functions of heparin sulfate proteoglycans in cell signaling during development. Development 131:6009–6021

    Article  CAS  Google Scholar 

  6. Bernfield M, Gotte M, Park P, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999) Functions of cell surface heparin sulfate proteoglycans. Annu Rev Biochem 68:729–777

    Article  CAS  Google Scholar 

  7. Greve H, Cully Z, Blumberg P, Kresse H (1988) Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts. J Biol Chem 263:12886–12892

    Article  CAS  Google Scholar 

  8. Calabro A, Hascall V (1994) Effects of brefeldin a on aggrecan core protein synthesis and maturation in rat chondrosarcoma cells. J Biol Chem 269:22771–22778

    Article  CAS  Google Scholar 

  9. Safaiyan F, Kolset S, Prydz K, Gottfridsson M, Lindahl U, Salmivirta M (1999) Selective effects of sodium chlorate treatment on the sulfation of heparin sulfate. J Biol Chem 274:36267–36273

    Article  CAS  Google Scholar 

  10. Uhlin-Hansen L, Yanagishita M (1993) Differential effect of brefeldin A on the biosynthesis of heparin sulfate and chondroitin/dermatan sulfate proteoglycans in rat ovarian granulosa cells in culture. J Biol Chem 268:17370–17376

    Article  CAS  Google Scholar 

  11. Sherwood A, Holmes E (1992) Brefeldin A induced inhibition of de novo globo- and neolacto-series glycolipid core chain biosynthesis in human cells. Evidence for an effect on beta 1➔4 galactosyltransferase activity. J Biol Chem 267:25328–25336

    Article  CAS  Google Scholar 

  12. Berkin A, Szarek W, Kisilevsky R (2005) Biological evaluation of a series of 2-acetoamido-2-deoxy-D-glucose analogs towards cellular glycosaminoglycan and protein synthesis in vitro. Glycoconj J 22:443–451

    Article  CAS  Google Scholar 

  13. Garud DR, Tran VM, Victor XV, Koketsu M, Kuberan B (2008) Inhibition of heparan sulfate and chondroitin sulfate proteoglycan biosynthesis. J Biol Chem 283:28881–28887

    Article  CAS  Google Scholar 

  14. Tsuzuki Y, Nguyen TK, Garud DR, Kuberan B, Koketsu M (2010) 4-Deoxy-4-fluoro-xyloside derivatives as inhibitors of glycosaminoglycan biosynthesis. Bioorg Med Chem Lett 20:7269–7273

    Article  CAS  Google Scholar 

  15. Wicki J, Schloegl J, Tarling CA, Withers SG (2007) Recruitment of both uniform and differential binding energy in enzymatic catalysis: xylanases from families 10 and 11. Biochemistry 46:6996–7005

    Article  CAS  Google Scholar 

  16. Chatron-Colliet A, Brusa C, Bertin-Jung I, Gulberti S, Ramalanjaona N, Fournel-Gigleux S, Brézillon S, Muzard M, Plantier-Royon R, Rémond C, Wegrowski Y (2017) ‘Click’-xylosides as initiators of the biosynthesis of glycosaminoglycans: comparison of mono-xylosides with xylobiosides. Chem Biol Drug Des 89:319–326

    Article  CAS  Google Scholar 

  17. Rossi L, Basu A (2005) Glycosidase inhibition by 1-glycosyl-4-phenyl triazoles. Bioorg Med Chem Lett 15:3596–3599

    Article  CAS  Google Scholar 

  18. Oshima N, Suzuki H, Morooka Y (1984) Synthesis and some reactions of dichloro(pentamethylcyclopentadienyl)ruthenium(III) oligomer. Chem Lett 13:1161–1164

    Article  Google Scholar 

  19. Mencioa CP, Garud DR, Doi Y, Bi Y, Vankayalapati H, Koketsu M, Kuberan B (2017) Ruthenium(II)- and copper(I)-catalyzed synthesis of click-xylosides and assessment of their glycosaminoglycan priming activity. Bioorg Med Chem Lett 27:5027–5030

    Article  Google Scholar 

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Acknowledgments

This work was supported in part by NIH grants (CA231093 and HL107152 to B.K), Human Frontier Science Program grant (RGP0044/2006 to B.K), and KAKENHI grant (No. 23590005 to M. K).

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Correspondence to Mamoru Koketsu .

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Mencio, C., Balagurunathan, K., Koketsu, M. (2022). Xyloside Derivatives as Molecular Tools to Selectively Inhibit Heparan Sulfate and Chondroitin Sulfate Proteoglycan Biosynthesis. In: Balagurunathan, K., Nakato, H., Desai, U., Saijoh, Y. (eds) Glycosaminoglycans. Methods in Molecular Biology, vol 2303. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1398-6_56

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  • DOI: https://doi.org/10.1007/978-1-0716-1398-6_56

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1397-9

  • Online ISBN: 978-1-0716-1398-6

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