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Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin
Author(s) -
VendrellNavarro Glòria,
Rúa Federico,
Bujons Jordi,
Brockmeyer Andreas,
Janning Petra,
Ziegler Slava,
Messeguer Angel,
Waldmann Herbert
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500169
Subject(s) - peptoid , tubulin , mitosis , microtubule , microbiology and biotechnology , chemistry , trimer , biochemistry , biophysics , biology , stereochemistry , peptide , dimer , organic chemistry
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.