Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin |
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| Authors: | Dr Glòria Vendrell‐Navarro Dr Federico Rúa Dr Jordi Bujons Andreas Brockmeyer Dr Petra Janning Dr Slava Ziegler Prof Dr Angel Messeguer Prof Dr Herbert Waldmann |
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| Affiliation: | 1. Department of Chemical Biology, Max‐Planck‐Institut für Molekulare Physiologie, Otto‐Hahn‐Strasse 11, 44227 Dortmund (Germany);2. Department of Biological Chemistry and Molecular Modeling, Institut de Química Avan?ada de Catalunya (IQAC‐CSIC), Jordi Girona 18–26, 08034 Barcelona (Spain);3. Lehrbereich Chemische Biologie, Fakult?t Chemie, Technische Universit?t Dortmund, Otto‐Hahn‐Strasse 6, 44227 Dortmund (Germany) |
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| Abstract: | We describe the synthesis of a library of 11 638 N‐alkylglycine peptoid trimers in a positional scanning format with adjustment of reaction conditions to account for different reactivities of the monomer building blocks. Evaluation of the library by high‐content phenotypic screening for modulators of the cytoskeleton and mitosis resulted in the identification of two apoptosis‐inducing peptoids, which, despite their structural similarity, target different proteins and cellular mechanisms. Whereas one peptoid binds to karyopherins, which mediate nuclear transport, the other N‐alkylglycine trimer binds tubulin at the vinca alkaloid binding site. |
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| Keywords: | apoptosis combinatorial chemistry peptidomimetics peptoids structure– activity relationships |
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