Structure, enzymatic stability and antitumor activity of sea lamprey GnRH-III and its dimer derivatives.
Direct antitumor activity of sea lamprey (Petromyzon marinus) gonadotropin-releasing hormone III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH(2); lGnRH-III) was described on several tumor cells. To improve the selectivity of antitumor effects without increasing the hormone releasing activity and to enhance the enzymatic stability, lGnRH-III dimers were prepared via disulfide bond formation. Our results demonstrate that the lGnRH-III dimer derivatives exhibited higher antiproliferative effect and enzymatic stability in comparison with the native lGnRH-III, while lower LH-releasing potency was determined. In order to find a correlation between the biological and structural features of these compounds, the conformation of lGnRH-III and its dimer derivatives was determined by ECD, VCD, FT-IR and (1)H NMR.
Mezo
Gábor
G
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, POB 32, 1518 Budapest 112, Hungary. gmezo@elte.hu
Czajlik
András
A
Manea
Marilena
M
Jakab
Annamária
A
Farkas
Viktor
V
Majer
Zsuzsa
Z
Vass
Elemér
E
Bodor
Andrea
A
Kapuvári
Bence
B
Boldizsár
Mariann
M
Vincze
Borbála
B
Csuka
Orsolya
O
Kovács
Magdolna
M
Przybylski
Michael
M
Perczel
András
A
Hudecz
Ferenc
F
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000378:metabolism; D002942:Circular Dichroism; D003198:Computer Simulation; D019281:Dimerization; D004795:Enzyme Stability; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007798:Lampreys / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared
D000970:Antineoplastic Agents; D009842:Oligopeptides; C448022:gonadotropin-releasing hormone-III; D007987:Gonadotropin-Releasing Hormone; D002918:Chymotrypsin; D011761:Pyrrolidonecarboxylic Acid