Synthesis and in vitro evaluation of new potent antagonists of growth hormone-releasing hormone (GH-RH)

Marta Zarandi, Magdolna Kovacs, Judit E. Horvath, Katalin Toth, Gabor Halmos, Kate Groot, Attila Nagy, Zoltan Kele, Andrew V. Schally

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

In the search of more potent antagonists of hGH-RH, 20 new analogs were synthesized, purified and tested in vitro. All the analogs were based on the N-terminal sequence of 28 or 29 amino acid residues of hGH-RH, but contained D-Arg2 and Nle27 modifications. Most analogs had Phe (pCl)6 and Agm29 substituents. The effect of other substitutions such as Abu8 and/or Abu15 and Ala-15 and various hydrophobic and hydrophilic D or L amino acids at position 8 were also investigated. All the peptides were acylated at the N- terminus in an attempt to increase the antagonistic activity. In the superfused rat pituitary cell system, most analogs inhibited more powerfully the GH release induced by GH-RH than the standard antagonist [Ac-Tyr1, D- Arg2]hGH-RH (1-29)-NH2. Some antagonists were long acting. Among the peptides synthesized, antagonist PhAc-[D-Arg2, Phe (pCl)6, Abu15, Nle27] hGH-RH (1-28) Agm (MZ-5-156) appeared to be the most potent and inhibited GH release in vitro 63-200 times more powerfully than the standard antagonist. MZ-5-156 and other antagonists showed high binding affinities to membrane receptors for GH-RH. Some of these hGH-RH antagonists could be further developed for possible oncological applications.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
JournalPeptides
Volume18
Issue number3
DOIs
StatePublished - Jun 9 1997
Externally publishedYes

Keywords

  • GH-RH antagonists
  • GH-RH receptor binding
  • Inhibitory activity of growth hormone-releasing hormone analogs (GH- RH)
  • Structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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    Zarandi, M., Kovacs, M., Horvath, J. E., Toth, K., Halmos, G., Groot, K., Nagy, A., Kele, Z., & Schally, A. V. (1997). Synthesis and in vitro evaluation of new potent antagonists of growth hormone-releasing hormone (GH-RH). Peptides, 18(3), 423-430. https://doi.org/10.1016/S0196-9781(96)00344-0