Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Blotting, Western
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cells, Cultured
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Chromatography, High Pressure Liquid
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Chymotrypsin / metabolism
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Circular Dichroism
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Computer Simulation
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Dimerization
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Enzyme Stability
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Gonadotropin-Releasing Hormone / chemistry*
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Gonadotropin-Releasing Hormone / metabolism
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Gonadotropin-Releasing Hormone / pharmacology*
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Humans
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Lampreys / metabolism*
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Magnetic Resonance Spectroscopy
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Models, Chemical
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Molecular Sequence Data
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Oligopeptides / chemistry*
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Oligopeptides / metabolism
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Oligopeptides / pharmacology*
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Protein Binding
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Pyrrolidonecarboxylic Acid / analogs & derivatives*
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Pyrrolidonecarboxylic Acid / chemistry
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Pyrrolidonecarboxylic Acid / metabolism
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Pyrrolidonecarboxylic Acid / pharmacology
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Rats
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Spectroscopy, Fourier Transform Infrared
Substances
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Antineoplastic Agents
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Oligopeptides
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gonadotropin-releasing hormone-III
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Gonadotropin-Releasing Hormone
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Chymotrypsin
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Pyrrolidonecarboxylic Acid