Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin

GLORIA VENDRELL-NAVARRO; FEDERICO RÚA; JORDI BUJONS; ANDREAS BROCKMEYER; PETRA JANNING; SLAVA ZIEGLER; ANGEL MESSEGUER; HERBERT WALDMANN

CHEMBIOCHEM

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2015 vol. 16 p. 1580 - 1587

1439-4227

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.