Head-to-Tail Cyclized Cystine-Knot Peptides by a Combined Recombinant and Chemical Route of Synthesis

Authors

  • Olga Avrutina Dr.,

    1. Institut für Organische Chemie und Biochemie, TU Darmstadt, Petersenstrasse 22, 64287 Darmstadt, Germany, Fax: (+49) 6151-165399
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    • These authors contributed equally to this work.

  • Hans-Ulrich Schmoldt Dr.,

    1. Institut für Organische Chemie und Biochemie, TU Darmstadt, Petersenstrasse 22, 64287 Darmstadt, Germany, Fax: (+49) 6151-165399
    2. Nascacell Technologies AG, Max-Lebsche-Platz 31, 81377 München, Germany
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    • These authors contributed equally to this work.

  • Dusica Gabrijelcic-Geiger Dr.,

    1. Abteilung für Klinische Chemie und Klinische Biochemie, Klinikum der Ludwig-Maximilians-Universität, Nussbaumstrasse 20, 80336 München, Germany
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  • Alexander Wentzel Dr.,

    1. Selecore GmbH, Marie Curie-Strasse 7, 37079 Göttingen, Germany
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  • Holm Frauendorf Dr.,

    1. Institut für Organische und Biomolekulare Chemie, Georg-August Universität Göttingen, Tamannstrasse 2, 37077 Göttingen, Germany, Fax: (+49) 551-392944
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  • Christian P. Sommerhoff Prof. Dr.,

    1. Abteilung für Klinische Chemie und Klinische Biochemie, Klinikum der Ludwig-Maximilians-Universität, Nussbaumstrasse 20, 80336 München, Germany
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  • Ulf Diederichsen Prof. Dr.,

    1. Institut für Organische und Biomolekulare Chemie, Georg-August Universität Göttingen, Tamannstrasse 2, 37077 Göttingen, Germany, Fax: (+49) 551-392944
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  • Harald Kolmar Prof. Dr.

    1. Institut für Organische Chemie und Biochemie, TU Darmstadt, Petersenstrasse 22, 64287 Darmstadt, Germany, Fax: (+49) 6151-165399
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Abstract

original image

Backbone cyclization of recombinantly produced cystine knot peptides, resulting in correctly folded macrocyclic disulfide-bridged peptides, is reported. It does not require protecting groups, takes place in aqueous solution, and is devoid of racemization and solubility problems. Scaling up to production of multimilligram amounts of iminocyclotides seems feasible. The resulting iminocyclotides are biologically active proteinase inhibitors—imino-cyclo-McoEeTIKKV was identified as the most potent proteinaceous inhibitor of human mast cell tryptase known.

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