Skip to main content

The hydrolysis of primary amide groups in Asn/Gln-containing peptides


Peptides Boc-Ala-Asn/Gln-OH and Boc-Asn/Gln-Ala-OH were saponified with barium hydroxide to corresponding Asp/Glu-containing peptides. Under the conditions of saponification, Boc-Asn-Ala-OH additionally afforded Boc-Asp-OH, isopeptide Boc-Asp(Ala)-OH, and Boc-NHSuc>Ala-OH, with the third being the key intermediate in these transformations. Boc-Asp(OMe)-Ala-OMe underwent similar transformations under treatment with diazomethane or triethylamine. Saponification with barium hydroxide was accompanied by a high epimerization ofN-terminal amino acid residues, whereas the products of the diazomethane treatment of Boc-Asp(OMe)-Ala-OMe had a low degree of epimerization.

This is a preview of subscription content, access via your institution.


  1. Richardson, J.S. and Richardson, D.C.,Prediction of Protein Structure and the Principles of Protein Conformation, Fasman, G.D., Ed., New York: Plenum, 1989, pp. 1–98.

    Google Scholar 

  2. Sondheimer, E. and Holley, R.W.,J. Am. Chem. Soc., 1954, vol. 76, pp. 2467–2470.

    Article  CAS  Google Scholar 

  3. Sondheimer, E. and Holley, R.W.,J. Am. Chem. Soc., 1957, vol. 79, pp. 3767–3770.

    Article  CAS  Google Scholar 

  4. Olsufyeva, E.N., Berdnikova, T.F., Miroshnikova, O.V., Reznikova, M.I., and Preobrazhenskaya, M.N.,J. Antibiot., 1999, vol. 52, pp. 319–324.

    PubMed  CAS  Google Scholar 

  5. Kemp, D.S.,The Peptides: Analysis, Synthesis, Biology. Vol. 1, Gross, E. and Meienhofer, J., Eds., New York: Academic, 1979, pp. 315–383.

    Google Scholar 

  6. Frank, H., Nicholson, G.J., and Bayer, E.,J. Chrom., 1978, vol. 146, pp. 197–206; 1978, vol. 167, pp. 187–196.

    Article  CAS  Google Scholar 

  7. Frank, H., Woiwode, W., Nicholson, G., and Bayer, E.,Liebigs Ann. Chem., 1981, pp. 354–365.

  8. Pozdnev, V.F.,Khim. Prir. Soedin., 1979, vol. 4, pp. 543–548.

    Google Scholar 

  9. Gershkovich, A.A. and Kibirev, V.K.,Sintez peptidov. Reagenty i metody (Synthesis of Peptides: Reagents and Methods), Kiev: Naukova Dumka, 1987.

    Google Scholar 

  10. Ono, N., Yamada, T., Saito, T., Tanaka, K., and Koji, A.,Bull. Chem. Soc. Jpn., 1978, vol. 51, pp. 2401–2404.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to V. V. Onoprienko.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Onoprienko, V.V., Yelin, E.A. & Miroshnikov, A.I. The hydrolysis of primary amide groups in Asn/Gln-containing peptides. Russ J Bioorg Chem 26, 361–368 (2000).

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI:

Key words

  • asparagine
  • aspartic acid
  • glutamine
  • glutamic acid
  • peptides
  • epimerization
  • rearrangement
  • primary amides
  • selective saponification