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Conformationally Homogeneous Heterocyclic Pseudotetrapeptides as Three-Dimensional Scaffolds for Rational Drug Design: Receptor-Selective Somatostatin Analogues

Authors

  • John M. Beierle,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2798
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  • W. Seth Horne Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2798
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  • Jan H. van Maarseveen Prof. Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2798
    2. Permanent address: Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam (The Netherlands)
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  • Beatrice Waser,

    1. Division of Cell Biology and Experimental Cancer Research, University of Berne, 3010 Berne (Switzerland)
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  • Jean Claude Reubi Prof. Dr.,

    1. Division of Cell Biology and Experimental Cancer Research, University of Berne, 3010 Berne (Switzerland)
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  • M. Reza Ghadiri Prof. Dr.

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2798
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  • We thank the NASA Earth and Space Science Fellowship Program (grant NNX07AR35H; J.M.B.), the Netherlands Organization for Scientific Research (NWO) for a travel grant (J.H.v.M.), and Dr. L. J. Leman for assistance with the manuscript. This research was supported in part by a grant from the National Institute of General Medical Sciences (GM52190) and by the Skaggs Institute for Chemical Biology.

Abstract

Amid-Ersatz: Ein 1,4-disubstituiertes 1,2,3-Triazol fungierte als Ersatz für eine trans-Amidbindung zur Erstellung einer Bibliothek von 16 diastereomeren Pseudotetrapeptiden als β-Turn-Mimetika. Eine Strukturanalyse bei hoher Auflösung zeigte, dass diese Gerüste charakteristische starre β-Turn-artige Strukturen mit homogener Konformation einnehmen (siehe Beispiel), von denen einige selektiv an Somatostatinrezeptoren binden und einige eine Breitbandaktivität zeigen.

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