Is lGnRH-III the most potent GnRH analog containing only natural amino acids that specifically inhibits the growth of human breast cancer cells?
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. lGnRH-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 lGnRH-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 lGnRH-III.
Herédi-Szabó
Krisztina
K
Department of Biomedical Sciences, School of Medicine, Creighton University, 2500 California Plaza, Omaha, Nebraska 68178-0405, USA.
Murphy
Richard F
RF
Lovas
Sándor
S
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C448022:gonadotropin-releasing hormone-III; D007987:Gonadotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid