Abstract
Based on rational design of the transition state analog inhibitors of glycosyltransferases, four model glycomimetics of this type, viz. benzyl 2-thio-α-dfructofuranoside 1-diethylphosphate (XIa), its β-anomer (XIb), and their ethyl 2-thio analogs — α-anomer (XIIa) and β-anomer (XIIb), were synthesized. In addition, fourteen precursors arising during the synthesis of the desired final model compounds (XI and XII), partially or fully acetylated benzyl and/or ethyl 2-thiofructofuranoside 1-diethyl phosphates, were isolated and characterized with the aim to prepare complete series of glycomimetics, representing donor UDP-GlcNAc designated for biological assays on human GnT’s, viz. GnT-I, Core2GnT, and GnT-V.
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References
Beyer, T. A., Sadler, J. E., Rearick, J. I., Paulson, J. C., & Hill, R. L. (1981) Glycosyltransferases and their use in assessing oligosaccharide structure and structure-function relationship. Advances in Enzymology and Related Areas of Molecular Biology, 52, 23–175. DOI: 10.1002/9780470122976.ch2.
Breton, C., Fournel-Gigleux, S., & Palcic, M. M. (2012) Recent structures, evolution and mechanisms of glycosyltransferases. Current Opinion in Structural Biology, 22, 540–549. DOI: 10.1016/j.sbi.2012.06.007.
Hadley, B., Maggioni, A., Ashikov, A., Day, C. J., Haselhorst, T., & Tiralongo, J. (2014) Structure and function of nucleotide sugar transporters: Current progress. Computational and Structural Biotechnology Journal, in press. DOI: 10.1016/j.csbj.2014.05.003.
Herzig, J., Nudelman, A., Gottlieb, H. E., & Fischer, B. (1986) Studies in sugar chemistry. 2. A simple method for O-deacetylation of polyacylated sugars. Journal of Organic Chemistry, 51, 727–730. DOI: 10.1021/jo00355a026.
Hirsch, J., Koóš, M., & Tvaroška, I. (2009) Synthesis of saccharide precursors for preparation of potential inhibitors of glycosyltransferases. Chemical Papers, 63, 329–335. DOI: 10.2478/s11696-009-0008-8.
Kleene, R., & Berger, E. G. (1993) The molecular and cell biology of glycosyltransferases. Biochimica et Biophysica Acta (BBA) — Reviews on Biomembranes, 1154, 283–325. DOI: 10.1016/0304-4157(93)90003-7.
Marquardt, T., & Freeze, H. (2001) Congenital disorders of glycosylation: Glycosylation defects in man and biological models for their study. Biological Chemistry, 382, 161–177.
Montreuil, J., Vliegenthart, J. F. G., & Schachter, H. (1995) Glycoproteins (Series: New comprehensive biochemistry, Vol. 29, Part A). Amsterdam, The Netherlands: Elsevier.
Montreuil, J., Vliegenthart, J. F. G., & Schachter, H. (1996) Glycoproteins and disease (Series: New comprehensive biochemistry, Vol. 30). Amsterdam, The Netherlands: Elsevier.
Raab, M., Kozmon, S., & Tvaroška, I. (2005) Potential transition-state analogs for glycosyltransferases. Design and DFT calculations of conformational behavior. Carbohydrate Research, 340, 1051–1057. DOI: 10.1016/j.carres.2005.01.041.
Sears, P., & Wong, C. H. (1999) Carbohydrate mimetics: A new strategy for tackling the problem of carbohydrate-mediated biological recognition. Angewandte Chemie International Edition, 38, 2300–2324. DOI: 10.1002/(SICI)1521-3773(19990816)38:16<2300::AID-ANIE2300>3.0.CO;2-6.
Waldscheck, B., Strieff, M., Notz, W., Kinzy, W., & Schmidt, R. R. (2001) α(1-3)-Galactosyltransferase inhibition based on a new type of disubstrate analogue. Angewandte Chemie International Edition, 40, 4007–4011. DOI: 10.1002/1521-3773(20011105)40:21<4007::AID-ANIE4007>3.0.CO;2-F.
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Baráth, M., Koóš, M., Tvaroška, I. et al. Synthesis of potential inhibitors of glycosyltransferases representing UDP-GlcNAc. Chem. Pap. 69, 339–347 (2015). https://doi.org/10.1515/chempap-2015-0017
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DOI: https://doi.org/10.1515/chempap-2015-0017