Skip to main content
SpringerLink
Log in

Development of transition state analogue inhibitors for N-acetylglycosyltransferases bearing dpsico- or dtagatofuranose scaffolds

  • Original Paper
  • Published:
Chemical Papers Aims and scope Submit manuscript

Abstract

New potential transition state analogue inhibitors for N-acetylglucosyltransferases (GnTs) were synthesised. These compounds based on psico- and tagatofuranose (structure) scaffold contained a 2-thiophenyl-1-O-diethylphosphate moiety mimicking the proposed model of the transition state of the enzymatic reaction catalysed by N-acetylglucosyltransferases. The synthesised compounds as well as their precursors were fully characterised by NMR, optical rotation and mass techniques. Anomeric configuration of tagatofuranose derivatives was confirmed by X-ray crystallography. Two types of potential human glycosyltransferase (GnTs) inhibitors representing donor UDP-GlcNAc, assigned for biological assays on human GnTs, were prepared.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bachmann, W. E., Ross, A., Dreiding, A. S., & Smith, P. A. S. (1954) Relative stabilities of cis-trans isomers of fused ring systems containing angular methyl groups. Journal of Organic Chemistry, 19, 222–240. DOI: 10.1021/jo01367a010.

    Article  CAS  Google Scholar 

  • Baráth, M., Koóš, M., Tvaroška, I., & Hirsch, J. (2015) Synthesis of glycomimetics of the inhibitors of glycosyltransferases representing UDP-GlcNAc. Chemical Papers, 2015, in press. DOI: 10.1515/chempap-2015-0017.

  • Collins, E. S., Galligan, M. C., Saldova, R., Adamczyk, B., Abrahams, J. L., Campbell, M. P., Ng, C. T., Veale, D. J., Murphy, T. B., Rudd, P. M., & FitzGerald, O. (2013) Glycosylation status of serum in inflammatory arthritis in response to anti-TNF treatment. Rheumatology, 52, 1572–1582. DOI: 10.1093/rheumatology/ket189.

    Article  CAS  Google Scholar 

  • Coutinho, P. M., Deleury, E., Davies, G. J., & Henrissat, B. (2003) An evolving hierarchical family classification for glycosyltransferases. Journal of Molecular Biology, 328, 307–317. DOI: 10.1016/s0022-2836(03)00307-3.

    Article  CAS  Google Scholar 

  • Dwek, R. A., Butters, T. D., Platt, F. M., & Zitzmann, N. (2002) Targeting glycosylation as a therapeutic approach. Nature Reviews Drug Discovery, 1, 65–75. DOI: 10.1038/nrd708.

    Article  CAS  Google Scholar 

  • Herve du Penhoat, P. C. M., & Perlin, A. S. (1974) A carbon 13 N.M.R. spectral study of dpsicose: anomeric and ringform equilibria of solutions of 2-hexaneuloses. Carbohydrate Research, 36, 111–120. DOI: 10.1016/s0008-6215(00)81996-5.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Hirsch, J., Koóš, M., & Tvaroška, I. (2009) Synthesis of saccharide precursors for preparation of potential inhibitors of glycosyltranferases. Chemical Papers, 63, 329–335. DOI: 10.2478/s11696-009-0008-8.

    Article  CAS  Google Scholar 

  • Kelley, J. L., McLean, E. W., Crouch, R. C., Averett, D. R., & Tuttle, J. V. (1995) [[(Guaninylalkyl)phosphinico]methyl] phosphonic acids. Multisubstrate analog inhibitors of human erythrocyte purine nucleoside phosphorylase. Journal of Medicinal Chemistry, 38, 1005–1014. DOI: 10.1021/jm00006a020.

    Article  CAS  Google Scholar 

  • Lairson, L. L., Henrissat, B., Davies, G. J., & Withers, S. G. (2008) Glycosyltransferases: Structures, functions, and mechanisms. Annual Reviews of Biochemistry, 77, 521–555. DOI: 10.1146/annurev.biochem.76.061005.092322.

    Article  CAS  Google Scholar 

  • Marquardt, T., & Freeze, H. (2001) Congenital disorders of glycosylation: Glycosylation defects in Man and biological models for their study. Biological Chemistry, 382, 161–177.

    Article  CAS  Google Scholar 

  • Matsumura, F., Tatsumi, S., Oka, N., & Wada, T. (2010) Rapid glycosylations under extremely mild acidic conditions. Use of ammonium salts to activate glycosyl phosphites via P-protonation. Carbohydrate Research, 345, 1211–1215. DOI: 10.1016/j.carres.2010.03.009.

    Article  CAS  Google Scholar 

  • Matulic-Adamic, J., Haeberli, P., & Usman, N. (1995) Synthesis of 5′-deoxy-5′-difluoromethyl phosphonate nucleotide analogs. Journal of Organic Chemistry, 60, 2563–2569. DOI: 10.1021/jo00113a040.

    Article  CAS  Google Scholar 

  • Montreuil, J., Vliegenthart, J. F. G., & Schachter, H. (1996) Glycoproteins and disease. Amsterdam, The Netherlands: Elsevier.

    Google Scholar 

  • Neuberger, A., & Deenen, L. L. M. (1995) Glycoproteins. (Vol. 29a). Amsterdam, The Netherlands: Elsevier.

    Google Scholar 

  • Pauling, L. (1948) Chemical achievement, and hope for the future. American Scientist, 36, 51–58.

    CAS  Google Scholar 

  • Perez, S., & Tvaroska, I. (2014) Carbohydrate-protein interactions — molecular modeling insights. Advances in Carbohydrate Chemistry and Biochemistry. submitted

  • Prisbe, E. J., Smejkal, J., Verheyden, J. P. H., & Moffatt, J. G. (1976) Halo sugar nucleosides. 5. Synthesis of angustmycin A and some base analogues. Journal of Organic Chemistry, 41, 1836–1846. DOI: 10.1021/jo00872a034.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Schramm, V. L. (1998) Enzymatic transition states and transition state analog design. Annual Reviews of Biochemistry, 67, 693–720. DOI: 10.1146/annurev.biochem.67.1.693.

    Article  CAS  Google Scholar 

  • Smith, M., Rammler, D. H., Goldberg, I. H., & Khorana, H. G. (1962) Studies on polynucleotides. XIV1 Specific synthesis of the C3″-C5″ interribonucleotide linkage. syntheses of uridylyl-(3″ → 5″)-uridine and uridylyl-(3″ → 5″)-adenosine2. Journal of the American Chemical Society, 84, 430–440. DOI: 10.1021/ja00862a023.

    Article  CAS  Google Scholar 

  • Stevens, F. J., & Argon, Y. (1999) Protein folding in the ER. Seminars in Cell & Developmental Biology, 10, 443–454. DOI: 10.1006/scdb.1999.0315.

    Article  CAS  Google Scholar 

  • Tvaroska, I. (2014) Atomistic insight into the catalytic mechanism of glycosyltransferases by combined quantum mechanics/molecular mechanics (QM/MM) methods. Carbohydrate Research. (in press).

  • Weis, W. I., Taylor, M. E., & Drickamer, K. (1998) The C-type lectin superfamily in the immune system. Immunologicals Reviews, 163, 19–34. DOI: 10.1111/j.1600-065X.1998.tb01185.x.

    Article  CAS  Google Scholar 

  • Wolfenden, R. (1969) Transition state analogues for enzyme catalysis. Nature, 223, 704–705. DOI: 10.1038/223704a0.

    Article  CAS  Google Scholar 

  • Yoshihara, A., Haraguchi, S., Gullapalli, P., Rao, D., Morimoto, K., Takata, G., Jones, N., Jenkinson, S. F., Wormald, M. R., Dwek, R. A., Fleet, G. W. J., & Izumori, K. (2008) Isomerization of deoxyhexaneoses: green bioproduction of 1-deoxy-dtagatose from lfucose and of 6-deoxy-dtagatose from dfucose using Enterobacter agglomerans strain 221e. Tetrahedron: Assymetry, 19, 739–745. DOI: 10.1016/j.tetasy.2008.02.013.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38, Bratislava, Slovakia

    Marek Baráth, Igor Tvaroška & Ján Hirsch

  2. Institute of Biological Chemistry, Academia Sinica, No. 128 Academia Road Sec. 2, Taipei, 11529, Taiwan

    Chun-Hung Lin

  3. Department of Chemistry, Faculty of Natural Sciences, Constantine The Philosopher University, 949 74, Nitra, Slovakia

    Igor Tvaroška

Authors
  1. Marek Baráth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Hung Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Igor Tvaroška
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ján Hirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marek Baráth.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baráth, M., Lin, CH., Tvaroška, I. et al. Development of transition state analogue inhibitors for N-acetylglycosyltransferases bearing dpsico- or dtagatofuranose scaffolds. Chem. Pap. 69, 348–357 (2015). https://doi.org/10.1515/chempap-2015-0063

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1515/chempap-2015-0063

Keywords

Search

Navigation