Synthesis and receptor binding of oxytocin analogs containing conformationally restricted amino acids |
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Authors: | Krisztina Bakos, Judit Havass, Ferenc Fü lö p, Lajos Gera, John M. Stewart, George Falkay Gá bor K. Tó th |
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Affiliation: | (1) Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary;(2) Department of Pharmacy and Biopharmacy, University of Szeged, Eötvös u. 6, Szeged, Hungary;(3) Department of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, Szeged, Hungary;(4) Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, U.S.A;(5) Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary |
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Abstract: | We report the solid-phase synthesis and receptor-binding properties of eleven oxytocin analogs (Mpa-Xxx-Ile-Gln-Asn-Cys-Sar-Arg-Gly-NH2) containing non-coded amino acids in position 2: D-- and L--(2-indanyl)glycine, R,S-6-methoxy-2-aminotetralin-2-carboxylic acid, D- and L-pentafluorophenylalanine, D,L-2,4-dimethylphenylalanine, D,L-2,4,6-trimethylphenylalanine, R,R- and S,S-1,2,3,4-tetrahydro-1-methyl--carboline-3-carboxylic acid and R- and S-1,2,3,4-tetrahydro--carboline-3-carboxylic acid. Some of these amino acid analogs (2-indanylglycine and D-pentafluorophenylalanine) were earlier successfully applied for the synthesis of potent bradykinin antagonists [1,2]. Their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The extent of binding of the peptides to the oxytocin receptor was in several cases was even higher than that of the parent hormone (oxytocin). However, the real pharmacological value of these analogs can be evaluated only after in vivo measurements of their inhibition of uterine motor activity. |
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Keywords: | /content/rb856e9pfndeu8ba/xxlarge945.gif" alt=" agr" align=" BASELINE" BORDER=" 0" >-(2-indanyl)glycine 1-methyltetrahydro- /content/rb856e9pfndeu8ba/xxlarge946.gif" alt=" beta" align=" MIDDLE" BORDER=" 0" >-carboline 6-methoxy-2-aminotetralin carboxylic acid differently substituted phenylalanine analogs tocolysis |
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