Advertisement

Applied Biochemistry and Microbiology

, Volume 55, Issue 1, pp 13–20 | Cite as

Spontaneous Proteolytic Processing of Human Recombinant Anti-Mullerian Hormone: Structural and Functional Differences of the Molecular Forms

  • A. Ya. RakEmail author
  • A. V. Trofimov
  • E. A. Protasov
  • S. V. Rodin
  • A. V. Zhahov
  • Ya. A. Zabrodskaya
  • A. M. Ischenko
Article
  • 3 Downloads

Abstract

The technology for the production of highly purified human recombinant anti-mullerian hormone (AMH)—a potential antitumor agent for the treatment of certain types of malignant neoplasms—is described. It was found that spontaneous proteolytic processing of the hormone is possible during the storage of AMH preparations under physiological conditions. This leads to the formation of C-terminal homodimer of AMH (activated form) and, later, to an inactive state during the further proteolysis. Sites at which spontaneous processing of the hormone molecule occurred during prolonged storage with the formation of active and inactive fragments were identified. The structural and functional differences in the molecular forms of the C-terminal fragment contained in the preparations are analyzed.

Keywords:

anti-mullerian hormone AMH chromatography MALDI mass-spectrometry monoclonal antibodies recombinant protein proteolysis 

Notes

COMPLIANCE WITH ETHICAL STANDARDS

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

REFERENCES

  1. 1.
    Gukasova, N.V. and Severin, S.E., Vopr. Biol. Med. Farm. Khim., 2005, no. 4, pp. 3–9.Google Scholar
  2. 2.
    Donahoe, P.K., Clarke, T., Teixeira, J., Maheswaran, S., and MacLaughlin, D.T., Mol. Cell. Endocrinol., 2003, vol. 211, no. 1, pp. 37–42.CrossRefGoogle Scholar
  3. 3.
    Jung, Y.S., Kim, H.J., Seo, S.K., Choi, Y.S., Nam, E.J., Kim, S.W., Han, H.D., Kim, J.W., and Kim, Y.T., Yonsei Med. J., 2016, vol. 57, no. 1, pp. 33–40.CrossRefGoogle Scholar
  4. 4.
    Pankhurst, M.W., Leathart, B.L., Batchelor, N.J., and McLennan, I.S., Endocrinology, 2016, vol. 157, no. 4, pp. 1622–1629.CrossRefGoogle Scholar
  5. 5.
    Di Clemente, N., Jamin, S.P., Lugovskoy, A., Carmillo, P., Ehrenfels, C., Picard, J.Y., Whitty, A., Josso, N., Pepinsky, R.B., and Cate, R.L., Mol. Endocrinol., 2010, vol. 24, no. 11, pp. 2193–2206.CrossRefGoogle Scholar
  6. 6.
    Nachtigal, M.W. and Ingraham, H.A., Proc. Natl. Acad. Sci. U. S. A., 1996, vol. 93, no. 15, pp. 7711–7716.CrossRefGoogle Scholar
  7. 7.
    Ragin, R.C., Donahoe, P.K., Kenneally, M.K., Ahmad, M.F., and MacLaughlin, D.T., Protein Expr. Purif., 1992, vol. 3, no. 3, pp. 236–245.CrossRefGoogle Scholar
  8. 8.
    Rak, A.Ya., Trofimov, A.V., Protasov, E.A., Simbirtsev, A.S., and Ishchenko, A.M., Ross. Immunol. Zh., 2017, vol. 11 (20), no. 4, pp. 755–757.Google Scholar
  9. 9.
    Pepinsky, R.B., Sinclair, L.K., Chow, E.P., Mattaliano, R.J., Manganaro, T.F., Donahoe, P.K., and Cate, R.L., J. Biol. Chem., 1988, vol. 263, no. 35, pp. 18961–18964.Google Scholar
  10. 10.
    Walker, J.M., Methods Mol. Biol., 1984, vol. 1, pp. 57–61.Google Scholar
  11. 11.
    Lorenzo, H.K., Teixeira, J., Pahlavan, N., Laurich, V.M., Donahoe, P.K., and MacLaughlin, D.T., J. Chromatogr. B, 2002, vol. 766, no. 1, pp. 89–98.CrossRefGoogle Scholar
  12. 12.
    Massagué, J., Annu. Rev. Biochem., 1998, vol. 67, no. 1, pp. 753–791.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2019

Authors and Affiliations

  • A. Ya. Rak
    • 1
    • 2
    Email author
  • A. V. Trofimov
    • 1
  • E. A. Protasov
    • 1
  • S. V. Rodin
    • 1
  • A. V. Zhahov
    • 1
  • Ya. A. Zabrodskaya
    • 1
    • 3
  • A. M. Ischenko
    • 1
  1. 1.State Research Institute of Highly Pure Biopreparations, Federal Medical-Biological Agency (FMBA)St. PetersburgRussia
  2. 2.St. Petersburg State UniversitySt. PetersburgRussia
  3. 3.Research Institute of Influenza, Ministry of Health of RussiaSt. PetersburgRussia

Personalised recommendations