1. Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin.
- Author
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Vendrell-Navarro G, Rúa F, Bujons J, Brockmeyer A, Janning P, Ziegler S, Messeguer A, and Waldmann H
- Subjects
- Cell Proliferation drug effects, HeLa Cells, Humans, Mitosis drug effects, Peptoids chemistry, Polymerization, Structure-Activity Relationship, Apoptosis drug effects, Karyopherins metabolism, Peptide Library, Peptoids chemical synthesis, Peptoids pharmacology, Tubulin metabolism
- 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., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
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