Abstract
Analogs of the decapeptide, gonadotropin-releasing hormone (GnRH), used in the treatment of hormone-dependent tumors, contain numerous unnatural amino acids, giving rise to many adverse effects. 1GnRH-III, a natural isoform of GnRH isolated from the sea lamprey, is a weak agonist of GnRH in the pituitary, but inhibits the growth of human cancer cells in micromolar concentrations. As 1GnRH-III is not a natural ligand in humans, it is possible that a more potent peptide, also containing only natural amino acids, can be synthesized. A positional scanning peptide library, focused on the variable region of the GnRH family of peptides, residues 5-8, was synthesized. The synthesized peptides were analyzed in competitive binding experiments and six new analogs were designed on the basis of the results. Their biological activities were evaluated in cell growth experiments. The only natural sequence selected was chicken GnRH-II. The synthetic library did not yield a more potent peptide than 1GnRH-III.
| Original language | English |
|---|---|
| Pages (from-to) | 714-720 |
| Number of pages | 7 |
| Journal | Journal of Peptide Science |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2006 |
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All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
Cite this
Is IGnRH-III the most potent GnRH analog containing only natural amino acids that specifically inhibits the growth of human breast cancer cells? / Herédi-Szabó, Krisztina; Murphy, Richard F.; Lovas, Sándor.
In: Journal of Peptide Science, Vol. 12, No. 11, 11.2006, p. 714-720.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Is IGnRH-III the most potent GnRH analog containing only natural amino acids that specifically inhibits the growth of human breast cancer cells?
AU - Herédi-Szabó, Krisztina
AU - Murphy, Richard F.
AU - Lovas, Sándor
PY - 2006/11
Y1 - 2006/11
N2 - Analogs of the decapeptide, gonadotropin-releasing hormone (GnRH), used in the treatment of hormone-dependent tumors, contain numerous unnatural amino acids, giving rise to many adverse effects. 1GnRH-III, a natural isoform of GnRH isolated from the sea lamprey, is a weak agonist of GnRH in the pituitary, but inhibits the growth of human cancer cells in micromolar concentrations. As 1GnRH-III is not a natural ligand in humans, it is possible that a more potent peptide, also containing only natural amino acids, can be synthesized. A positional scanning peptide library, focused on the variable region of the GnRH family of peptides, residues 5-8, was synthesized. The synthesized peptides were analyzed in competitive binding experiments and six new analogs were designed on the basis of the results. Their biological activities were evaluated in cell growth experiments. The only natural sequence selected was chicken GnRH-II. The synthetic library did not yield a more potent peptide than 1GnRH-III.
AB - Analogs of the decapeptide, gonadotropin-releasing hormone (GnRH), used in the treatment of hormone-dependent tumors, contain numerous unnatural amino acids, giving rise to many adverse effects. 1GnRH-III, a natural isoform of GnRH isolated from the sea lamprey, is a weak agonist of GnRH in the pituitary, but inhibits the growth of human cancer cells in micromolar concentrations. As 1GnRH-III is not a natural ligand in humans, it is possible that a more potent peptide, also containing only natural amino acids, can be synthesized. A positional scanning peptide library, focused on the variable region of the GnRH family of peptides, residues 5-8, was synthesized. The synthesized peptides were analyzed in competitive binding experiments and six new analogs were designed on the basis of the results. Their biological activities were evaluated in cell growth experiments. The only natural sequence selected was chicken GnRH-II. The synthetic library did not yield a more potent peptide than 1GnRH-III.
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U2 - 10.1002/psc.783
DO - 10.1002/psc.783
M3 - Article
VL - 12
SP - 714
EP - 720
JO - Journal of Peptide Science
JF - Journal of Peptide Science
SN - 1075-2617
IS - 11
ER -