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Design and synthesis of a gonadotropin-releasing hormone (GnRH) analogue, [Tyr(OMe)5,d-Glu6,Aze9]GnRH: Receptor binding, gonadotropin release and ovulation studies

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Summary

Gonadotropin-releasing hormone (GnRH) stimulates the release and synthesis of gonadotropin hormones (GtH) and is the key regulator of reproduction. The present study was carried out to design a potent GnRH analogue containing Tyr(OMe) at position 5 and ad-amino acid at position 6. This was based on a previous study in which [Tyr(OMe)5]GnRH was shown to have reduced potency compared to GnRH. A novel GnRH peptide containing Tyr(OMe)5 andd-Glu6 in combination with other substitutions at positions 9 and 10 was synthesized in the present study and tested for binding to the rat pituitary as well as potency in terms of gonadotropin (GtH) release in the goldfish pituitary and ovulation in sea bass. The results demonstrate that the replacement of the glycine residue at position 6 with ad-Glu in combination with the substitution of proline at position 9 with azetidine (Aze) increased the binding and biological activity of [Tyr(OMe)5]GnRH. The observed increased potency is likely to be related to the improved resistance to degradation. The present findings may lead to the development of a more potent GnRH agonist for inducing ovulation in fish.

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Authors and Affiliations

  1. Department of Chemistry, University of Patras, 26500, Patras, Greece

    Maria Keramida, John M. Matsoukas, Dimitris Panagiotopoulos, Kostas Alexopoulos & Elizabeth Matsoukas

  2. Thalassa Fish Hatchery, 33056 Hiliadou Doridos, Greece

    John Cladas

  3. Department of Obstetrics and Gynecology, Rion University Hospital, University of Patras, 26500, Patras, Greece

    Vasilis A. Tzingounis & Emmanuel Cardamakis

  4. Department of Chemistry, University of Minho, Gualtar, P-4700, Braga, Portugal

    Hernâni L. S. Maia

  5. Department of Biological Sciences, The University of Calgary, 2500 University Drive N.W., T2N 4NI, Calgary, AB, Canada

    Debanaba Pati & Hamid R. Habibi

  6. Department of Pharmacology and Therapeutics, The University of Calgary, 3330 Hospital Drive N.W., T2N 4NI, Calgary, AB, Canada

    Hamid R. Habibi

Authors
  1. Maria Keramida
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  2. John M. Matsoukas
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  3. Dimitris Panagiotopoulos
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  4. Kostas Alexopoulos
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  5. Elizabeth Matsoukas
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  6. John Cladas
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  7. Vasilis A. Tzingounis
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  8. Emmanuel Cardamakis
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  9. Hernâni L. S. Maia
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  10. Debanaba Pati
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  11. Hamid R. Habibi
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Keramida, M., Matsoukas, J.M., Panagiotopoulos, D. et al. Design and synthesis of a gonadotropin-releasing hormone (GnRH) analogue, [Tyr(OMe)5,d-Glu6,Aze9]GnRH: Receptor binding, gonadotropin release and ovulation studies. Lett Pept Sci 3, 257–262 (1996). https://doi.org/10.1007/BF00128117

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  • DOI: https://doi.org/10.1007/BF00128117

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