Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin
作者： Glòria Vendrell-Navarro , Federico Rúa , Jordi Bujons , Andreas Brockmeyer , Petra Janning
关键词: Tubulin 、 Cytoskeleton 、 Stereochemistry 、 Biology 、 Biophysics 、 Karyopherins 、 Structural similarity 、 Peptidomimetic 、 Nuclear transport 、 Peptoid 、 Binding site
摘要: We describe the synthesis of a library 11, 638 N-alkylglycine peptoid trimers in positional scanning format with adjustment reaction conditions to account for different reactivities monomer building blocks. Evaluation by high-content phenotypic screening modulators cytoskeleton and mitosis resulted identification two apoptosis-inducing peptoids, which, despite their structural similarity, target proteins cellular mechanisms. Whereas one binds karyopherins, which mediate nuclear transport, other trimer tubulin at vinca alkaloid binding site.
mpg.de
core.ac.uk 
sci-hub.se 参考文章(52)
Jacqueline Shukaliak Quandt, Eva Borras, Elisabetta Prat, Harald Gelderblom, Richard A Houghten, Azita Kashani, Clemencia Pinilla, Claus-Steffen Stuerzebecher, Roland Martin, Peptidic complex mixtures as therapeutic agents in CNS autoimmunity Molecular Immunology. ,vol. 40, pp. 1075- 1087 ,(2004) , 10.1016/J.MOLIMM.2003.11.006
Christine M. Oslowski, Fumihiko Urano, Measuring ER Stress and the Unfolded Protein Response Using Mammalian Tissue Culture System The Unfolded Protein Response and Cellular Stress, Part B. ,vol. 490, pp. 71- 92 ,(2011) , 10.1016/B978-0-12-385114-7.00004-0
D. Gomika Udugamasooriya, Sean P. Dineen, Rolf A. Brekken, Thomas Kodadek, A Peptoid "Antibody Surrogate" That Antagonizes VEGF Receptor 2 Activity Journal of the American Chemical Society. ,vol. 130, pp. 5744- 5752 ,(2008) , 10.1021/JA711193X
Miriam Corredor, Jordi Bujons, Mar Orzáez, Mónica Sancho, Enrique Pérez-Payá, Ignacio Alfonso, Angel Messeguer, Optimizing the control of apoptosis by amide/triazole isosteric substitution in a constrained peptoid. European Journal of Medicinal Chemistry. ,vol. 63, pp. 892- 896 ,(2013) , 10.1016/J.EJMECH.2013.03.004
Yong-Uk Kwon, Thomas Kodadek, Quantitative evaluation of the relative cell permeability of peptoids and peptides. Journal of the American Chemical Society. ,vol. 129, pp. 1508- 1509 ,(2007) , 10.1021/JA0668623
Kate J. Reilley, Marc Giulianotti, Colette T. Dooley, Adel Nefzi, Jay P. McLaughlin, Richard A. Houghten, Identification of two novel, potent, low-liability antinociceptive compounds from the direct in vivo screening of a large mixture-based combinatorial library. Aaps Journal. ,vol. 12, pp. 318- 329 ,(2010) , 10.1208/S12248-010-9191-3
Jonathan F. Soderholm, Stephen L. Bird, Petr Kalab, Yasaswini Sampathkumar, Keisuke Hasegawa, Michael Uehara-Bingen, Karsten Weis, Rebecca Heald, Importazole, a Small Molecule Inhibitor of the Transport Receptor Importin-β ACS Chemical Biology. ,vol. 6, pp. 700- 708 ,(2011) , 10.1021/CB2000296
Rebecca C. Taylor, Sean P. Cullen, Seamus J. Martin, Apoptosis: controlled demolition at the cellular level Nature Reviews Molecular Cell Biology. ,vol. 9, pp. 231- 241 ,(2008) , 10.1038/NRM2312
Nobuaki Kudo, Barbara Wolff, Toshihiro Sekimoto, Erwin P. Schreiner, Yoshihiro Yoneda, Mitsuhiro Yanagida, Sueharu Horinouchi, Minoru Yoshida, Leptomycin B Inhibition of Signal-Mediated Nuclear Export by Direct Binding to CRM1 Experimental Cell Research. ,vol. 242, pp. 540- 547 ,(1998) , 10.1006/EXCR.1998.4136
Asako Sakaue-Sawano, Hiroshi Kurokawa, Toshifumi Morimura, Aki Hanyu, Hiroshi Hama, Hatsuki Osawa, Saori Kashiwagi, Kiyoko Fukami, Takaki Miyata, Hiroyuki Miyoshi, Takeshi Imamura, Masaharu Ogawa, Hisao Masai, Atsushi Miyawaki, Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression Cell. ,vol. 132, pp. 487- 498 ,(2008) , 10.1016/J.CELL.2007.12.033