Skip to main content
SpringerLink
Log in

Synthesis and X-ray crystallographic investigation of N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)alkanamides as analogs of N-glycoprotein linkage region

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

As part of our ongoing program aimed at understanding the structural significance of GlcNAcβAsn linkage conserved in all eukaryotic N-glycoproteins, the present study reports on the synthesis and X-ray crystal structures of N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)acetamide (Glc3NAcβNHAc) and the corresponding propionamide (Glc3NAcβNHPr). Comparative analysis of these structures with those of the corresponding GlcNAc (C2 acetamido) compounds showed that the bifurcated anti-parallel pattern involving N–H…O and C–H…O hydrogen bonds, the hallmark feature of the N-glycoprotein models, GlcNAcβNHAc and GlcNAcβAsn, is absent in both the C3 acetamido analogs. The extended (anti) conformation of the amido aglycon moiety as defined by χ 2 seen in the case of C2 acetamido derivative, GlcNAcβNHPr, turns into gauche for the C3 acetamido analog (Glc3NAcβNHPr). This observation is consistent with the earlier work on the critical role of the C2-NHAc group of GlcNAcβAsn in controlling χ 2 at the linkage region of N-glycoproteins.

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

Fig. 1
Fig. 2
Scheme 1
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

Glc3NAcβNHAc:

N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)acetamide

Glc3NAcβNHPr:

N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)propionamide

NMR:

Nuclear Magnetic Resonance

ESI-MS:

Electrospray Ionization Mass Spectrometry

ORTEP:

Oak Ridge Thermal Ellipsoid Plot

References

  1. Varki, A.: Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3, 97–130 (1993)

    Article  PubMed  CAS  Google Scholar 

  2. Spiro, R.G.: Protein glycosylation: nature, distribution, enzymatic formation, and disease implication of glycopeptide bonds. Glycobiology 12, 43R–56R (2002)

    Article  PubMed  CAS  Google Scholar 

  3. Ohanessian, J., Avenel, D., Neuman, A., Gillier-Pandraud, H.: Structure cristalline de la 2- acétamido-1-N-(L-aspart-4-oyl)-2-désoxy-β-D-glucopyranosylamine. Carbohydr. Res. 80, 1–13 (1980)

    Article  CAS  Google Scholar 

  4. Sriram, D., Lakshmanan, T., Loganathan, D., Srinivasan, S.: Crystal structure of a hydrated N-glycoprotein linkage region model and its analogue: hydrogen bonding and π-π stacking driven molecular assembly. Carbohydr. Res. 309, 227–236 (1998)

    Article  CAS  Google Scholar 

  5. Lakshmanan, T., Sriram, D., Priya, K., Loganathan, D.: On the structural significance of the linkage region constituents of N-glycoproteins: an X-ray crystallographic investigation using models and analogs. Biochem. Biophys. Res. Commun. 312, 405–413 (2003)

    Article  PubMed  CAS  Google Scholar 

  6. Loganathan, D., Aich, U.: Observation of a unique pattern of bifurcated hydrogen bonds in the crystal structures of the N-glycoprotein linkage region models. Glycobiology 16, 343–348 (2006)

    Article  PubMed  CAS  Google Scholar 

  7. Cioci, G., Srivastava, A., Loganathan, D., Mason, S.A., Pérez, S., Imberty, A.: Low temperature neutron diffraction structures of N-glycoprotein linkage models and analogs: structure refinement and trifurcated hydrogen bonds. J. Am. Chem. Soc. 133, 10042–10045 (2011)

    Article  PubMed  CAS  Google Scholar 

  8. Mohamed Naseer Ali, M., Aich, U., Varghese, B., Pérez, S., Imberty, A., Loganathan, D.: Conformational preferences of the aglycon moiety in models and analogs of GlcNAc-Asn linkage: crystal structures and ab initio quantum chemical calculations of N-(β-D -glycopyranosyl)haloacetamides. J. Am. Chem. Soc. 130, 8317–8325 (2008)

    Article  Google Scholar 

  9. Muhizi, T., Grelier, S., Coma, V.: Synthesis and antibacterial activity of aminodeoxyglucose derivatives against Listeria innocua and Salmonella typhimurium. J. Agric. Food Chem. 57, 8770–8775 (2009)

    Article  PubMed  CAS  Google Scholar 

  10. Barton, D.H.R., Jaszberenyi, J.C., Theodorakis, E.A., Reibenspiest, J.H.: The invention of radical reactions. 30. diazirines as carbon radical traps. Mechanistic aspects and synthetic applications of a novel and efficient amination process. J. Am. Chem. Soc. 115, 8050–8059 (1993)

    Article  CAS  Google Scholar 

  11. Bruker SADABS, Bruker AXS Inc., Madison, Wisconsin, USA (1999)

  12. Sheldrick, G.M. SHELXL97, Program for Crystal Structure Refinement; University of Gottingen, Germany (1997)

  13. Farrugia, L.J.: ORTEP-3 for Windows-a version of ORTEP-III with a Graphical User Interface (GUI). J. Appl. Cryst. 30, 565 (1997)

    Article  CAS  Google Scholar 

  14. Bruno, I.J., Cole, J.C., Edgington, P.R., Kessler, M., Macrae, C.F., McCabe, P., Pearson, J., Taylor, R.: New software for searching the Cambridge Structural Database and visualizing crystal structure. Acta Cryst. B58, 389–397 (2002)

    CAS  Google Scholar 

  15. Delbaere, L.T.J.: The molecular and crystal structures of 4-N-(2-acetamido-2-deoxy-β-D -glucopyranosyl)-L-asparagine trihydrate and 4-N-(β-D-glucopyranosyl)-L-asparagine monohydrate. The X-ray analysis of a carbohydrate-peptide linkage. Biochem. J. 143, 197–205 (1974)

    PubMed  CAS  Google Scholar 

  16. Marchessault, R.H., Perez, S.: Conformations of the hydroxymethyl group in crystalline aldohexopyranoses. Biopolymers 18, 2369–2374 (1979)

    Article  CAS  Google Scholar 

  17. Larkin, A., Imperiali, B.: The expanding horizons of asparagine-linked glycosylation. Biochemistry 50, 4411–4426 (2011)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The funding provided by Department of Science and Technology (DST), New Delhi for the purchase of the 400 MHz NMR under IRHPA Scheme and ESI-MS under the FIST program to the Department of Chemistry, IIT Madras is gratefully acknowledged. The authors thank the single crystal XRD facility, Chemistry Department, IIT Madras for the X-ray data collection. We are thankful to Mr. V. Ram Kumar for X-ray data collection. One of us (M.M) is thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi, for the award of a Senior Research Fellowship. We also thank Cambridge Crystallographic Data Centre (CCDC), United Kingdom, for making the program Mercury 2.3 available for use.

Supplementary

Data Complete structural data of the Glc3NAcβNHAc (3) and Glc3NAcβNHPr (4) have been deposited at the Cambridge Crystallographic Data Centre (CCDC # 840488 – 840489, respectively), and can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif (or from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44-1223-336033; or email: deposit@ccdc.cam.ac.uk).

Author information

Authors and Affiliations

  1. Department of Chemistry, Indian Institute of Technology Madras, Chennai, 600036, India

    Manoharan Mathiselvam & Duraikkannu Loganathan

  2. Sophisticated Analytical Instrumentation Facility, Indian Institute of Technology Madras, Chennai, 600036, India

    Babu Varghese

Authors
  1. Manoharan Mathiselvam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Babu Varghese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Duraikkannu Loganathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Duraikkannu Loganathan.

Additional information

Dedicated to late Prof. Nathan Sharon

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mathiselvam, M., Varghese, B. & Loganathan, D. Synthesis and X-ray crystallographic investigation of N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)alkanamides as analogs of N-glycoprotein linkage region. Glycoconj J 28, 573–580 (2011). https://doi.org/10.1007/s10719-011-9357-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-011-9357-y

Keywords

Search

Navigation