Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin-releasing hormone (GnRH)-III analogs

Magdolna Kovács, B. Vincze, J. Horváth, J. Seprődi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

GnRH-III was reported to have selective FSH-releasing activity in rats and significant anticancer potency on human breast cancer cells. To improve either of these effects, 14 analogs were synthesized and investigated for FSH/LH stimulation and breast cancer inhibition. Analogs with single amino acid changes in positions 5-7 or 10 showed small or no difference in the FSH- or LH-releasing activity compared with GnRH-III but their anticancer potency decreased significantly. Modification of the terminal amino acids, side chain cyclization at the 6-8 regions, or combined amino acid changes at positions 4, 6 and/or 8 resulted in the decrease of both effects. Gonadotropin-releasing activity of Arg8-GnRH-III was improved 3-11-fold. A copolymer conjugate of GnRH-III showed 2-3-fold anticancer activity while losing endocrine potency. Conclusion: The activation of GnRH-receptors on pituitary and breast cancer cells requires a specific structure and/or conformation that makes possible to improve the anticancer selectivity of GnRH analogs.

Original languageEnglish
Pages (from-to)821-829
Number of pages9
JournalPeptides
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Breast Neoplasms
Amino Acids
Cells
LHRH Receptors
Cyclization
Pituitary Neoplasms
Gonadotropins
Gonadotropin-Releasing Hormone
Conformations
Rats
Copolymers
Chemical activation
gonadotropin-releasing hormone-III

Keywords

  • Anticancer selectivity
  • Breast cancer
  • Copolymer conjugate
  • Structural changes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

@article{eaefacebf8044027b008be46c9a80a5b,
title = "Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin-releasing hormone (GnRH)-III analogs",
abstract = "GnRH-III was reported to have selective FSH-releasing activity in rats and significant anticancer potency on human breast cancer cells. To improve either of these effects, 14 analogs were synthesized and investigated for FSH/LH stimulation and breast cancer inhibition. Analogs with single amino acid changes in positions 5-7 or 10 showed small or no difference in the FSH- or LH-releasing activity compared with GnRH-III but their anticancer potency decreased significantly. Modification of the terminal amino acids, side chain cyclization at the 6-8 regions, or combined amino acid changes at positions 4, 6 and/or 8 resulted in the decrease of both effects. Gonadotropin-releasing activity of Arg8-GnRH-III was improved 3-11-fold. A copolymer conjugate of GnRH-III showed 2-3-fold anticancer activity while losing endocrine potency. Conclusion: The activation of GnRH-receptors on pituitary and breast cancer cells requires a specific structure and/or conformation that makes possible to improve the anticancer selectivity of GnRH analogs.",
keywords = "Anticancer selectivity, Breast cancer, Copolymer conjugate, Structural changes",
author = "Magdolna Kov{\'a}cs and B. Vincze and J. Horv{\'a}th and J. Seprődi",
year = "2007",
month = "4",
doi = "10.1016/j.peptides.2007.01.003",
language = "English",
volume = "28",
pages = "821--829",
journal = "Peptides",
issn = "0196-9781",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin-releasing hormone (GnRH)-III analogs

AU - Kovács, Magdolna

AU - Vincze, B.

AU - Horváth, J.

AU - Seprődi, J.

PY - 2007/4

Y1 - 2007/4

N2 - GnRH-III was reported to have selective FSH-releasing activity in rats and significant anticancer potency on human breast cancer cells. To improve either of these effects, 14 analogs were synthesized and investigated for FSH/LH stimulation and breast cancer inhibition. Analogs with single amino acid changes in positions 5-7 or 10 showed small or no difference in the FSH- or LH-releasing activity compared with GnRH-III but their anticancer potency decreased significantly. Modification of the terminal amino acids, side chain cyclization at the 6-8 regions, or combined amino acid changes at positions 4, 6 and/or 8 resulted in the decrease of both effects. Gonadotropin-releasing activity of Arg8-GnRH-III was improved 3-11-fold. A copolymer conjugate of GnRH-III showed 2-3-fold anticancer activity while losing endocrine potency. Conclusion: The activation of GnRH-receptors on pituitary and breast cancer cells requires a specific structure and/or conformation that makes possible to improve the anticancer selectivity of GnRH analogs.

AB - GnRH-III was reported to have selective FSH-releasing activity in rats and significant anticancer potency on human breast cancer cells. To improve either of these effects, 14 analogs were synthesized and investigated for FSH/LH stimulation and breast cancer inhibition. Analogs with single amino acid changes in positions 5-7 or 10 showed small or no difference in the FSH- or LH-releasing activity compared with GnRH-III but their anticancer potency decreased significantly. Modification of the terminal amino acids, side chain cyclization at the 6-8 regions, or combined amino acid changes at positions 4, 6 and/or 8 resulted in the decrease of both effects. Gonadotropin-releasing activity of Arg8-GnRH-III was improved 3-11-fold. A copolymer conjugate of GnRH-III showed 2-3-fold anticancer activity while losing endocrine potency. Conclusion: The activation of GnRH-receptors on pituitary and breast cancer cells requires a specific structure and/or conformation that makes possible to improve the anticancer selectivity of GnRH analogs.

KW - Anticancer selectivity

KW - Breast cancer

KW - Copolymer conjugate

KW - Structural changes

UR - http://www.scopus.com/inward/record.url?scp=33847405729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847405729&partnerID=8YFLogxK

U2 - 10.1016/j.peptides.2007.01.003

DO - 10.1016/j.peptides.2007.01.003

M3 - Article

VL - 28

SP - 821

EP - 829

JO - Peptides

JF - Peptides

SN - 0196-9781

IS - 4

ER -