Bicyclic Peptides with Optimized Ring Size Inhibit Human Plasma Kallikrein and its Orthologues While Sparing Paralogous Proteases

Authors

  • Dr. Vanessa Baeriswyl,

    1. Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH B3 391, Station 6, 1015 Lausanne (Switzerland)
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  • Dr. Helen Rapley,

    1. Bicycle Therapeutics Ltd., Meditrina Building, Babraham Research Campus, Cambridge, CB22 3AT (UK)
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  • Lisa Pollaro,

    1. Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH B3 391, Station 6, 1015 Lausanne (Switzerland)
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  • Dr. Catherine Stace,

    1. Bicycle Therapeutics Ltd., Meditrina Building, Babraham Research Campus, Cambridge, CB22 3AT (UK)
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  • Dr. Dan Teufel,

    1. Bicycle Therapeutics Ltd., Meditrina Building, Babraham Research Campus, Cambridge, CB22 3AT (UK)
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  • Dr. Edward Walker,

    1. Bicycle Therapeutics Ltd., Meditrina Building, Babraham Research Campus, Cambridge, CB22 3AT (UK)
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  • Shiyu Chen,

    1. Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH B3 391, Station 6, 1015 Lausanne (Switzerland)
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  • Sir Greg Winter,

    Corresponding author
    1. Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 0QH (UK)
    • Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 0QH (UK)
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  • Dr. John Tite,

    Corresponding author
    1. Bicycle Therapeutics Ltd., Meditrina Building, Babraham Research Campus, Cambridge, CB22 3AT (UK)
    • Bicycle Therapeutics Ltd., Meditrina Building, Babraham Research Campus, Cambridge, CB22 3AT (UK)
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  • Prof. Christian Heinis

    Corresponding author
    1. Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH B3 391, Station 6, 1015 Lausanne (Switzerland)
    • Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), CH B3 391, Station 6, 1015 Lausanne (Switzerland)
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Abstract

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Picky push-bikes! Bicyclic peptides with low to sub-nanomolar inhibitory activities towards the serine protease plasma kallikrein were developed. By modulating the size of the macrocyclic rings, inhibitors with the desired specificity profile could be generated.

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