HUMAN RECOMBINANT ANTI-MULLERIAN HORMONE: A SELF-ACTIVATING DRUG

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Abstract

Here, the autoproteolytic activity of human recombinant anti-Mullerian hormone (rAMH), a potential antineoplastic drug, was investigated. It was shown that the hormone is not only able to activate itself by the limited proteolysis, but also specifically interacts with the proteolytic inhibitor aprotinin. The involvement of the rAMH specific proteolysis site in interaction with a specifi c receptor type II (MISRII) was found. The data obtained may be useful to clarify some aspects of the native AMH biochemistry and pharmacodynamics of the recombinant hormone.

About the authors

A. Ya. Rak

State Research Institute for Highly Pure Biopreparations;
Saint-Petersburg State University

Author for correspondence.
Email: a.ya.rak@hpb.spb.ru

Junior Researcher of the Protein Biochemistry Laboratory;

PhD student,

St. Petersburg

Russian Federation

A. V. Trofimov

State Research Institute for Highly Pure Biopreparations

Email: fake@neicon.ru

Group Head of the Protein Biochemistry Laboratory,

St. Petersburg

Russian Federation

A. M. Ischenko

State Research Institute for Highly Pure Biopreparations

Email: fake@neicon.ru

PhD, Head of the Protein Biochemistry Laboratory,

St. Petersburg

Russian Federation

References

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  2. Jung Y. S., Kim H. J., Seo S. K., Choi Y. S., Nam E. J., Kim S. W., Han H. D., Kim J. W., Kim Y. T. Anti-proliferative and apoptotic activities of Müllerian inhibiting substance combined with calcitriol in ovarian cancer cell lines. Yonsei Med J. 2016, 57(1), 33–40.
  3. Di Clemente N., Jamin S. P., Lugovskoy A., Carmillo P., Ehrenfels C., Picard J. Y., Whitty A., Josso N., Pepinsky R. B., Cate R. L. Processing of anti-mullerian hormone regulates receptor activation by a mechanism distinct from TGF-β. Mol Endocrinol. 2010, 24(11), 2193–2206.
  4. Rak A. Ya., Trofi mov A. V., Protasov E. A., Rodin S. V., Zhakhov A. V., Zabrodskaya Ya. A., Ischenko A. M. Spontaneous proteolytic processing of human recombinant anti-mullerian hormone: structural and functional differences of the molecular forms. Appl Biochem Microbiol. 2019, 55(1),13–20.
  5. Рак А. Я., Трофимов А. В., Колобов А. А., Ищенко А. М. Моноклональные антитела против С-концевого фрагмента рекомбинантного антимюллерова гормона человека: инструмент для очистки, детекции и исследования. Цитокины и воспаление. 2018, 17(1–4), 72–79.
  6. Rak A. Ya., Trofimov A. V., Pigareva N. V., Simbirtsev A. S., Ischenko A. M. The cytotoxic effect of activated recombinant anti-mullerian hormone as a basis for the development of a new drug. Cell Tissue Biol. 2018, 12(6), 460–467.

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Copyright (c) 2019 Rak A.Y., Trofimov A.V., Ischenko A.M.

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