@Article{duepublico_mods_00078019,
  author = 	{Meiners, Annika
		and B{\"a}cker, Sandra
		and Hadrovi{\'{c}}, Inesa
		and Heid, Christian
		and Beuck, Christine
		and Ruiz-Blanco, Yasser B.
		and Mieres-Perez, Joel
		and P{\"o}rschke, Marius
		and Grad, Jean-No{\"e}l
		and Vallet, Cecilia
		and Hoffmann, Daniel
		and Bayer, Peter
		and S{\'a}nchez-Garc{\'i}a, Elsa
		and Schrader, Thomas
		and Knauer, Shirley K.},
  title = 	{Specific inhibition of the Survivin--CRM1 interaction by peptide-modified molecular tweezers},
  year = 	{2021},
  month = 	{Mar},
  day = 	{08},
  keywords = 	{Cancer; Chemical biology; Chemistry; Molecular biology},
  abstract = 	{Survivin's dual function as apoptosis inhibitor and regulator of cell proliferation is mediated via its interaction with the export receptor CRM1. This protein--protein interaction represents an attractive target in cancer research and therapy. Here, we report a sophisticated strategy addressing Survivin's nuclear export signal (NES), the binding site of CRM1, with advanced supramolecular tweezers for lysine and arginine. These were covalently connected to small peptides resembling the natural, self-complementary dimer interface which largely overlaps with the NES. Several biochemical methods demonstrated sequence-selective NES recognition and interference with the critical receptor interaction. These data were strongly supported by molecular dynamics simulations and multiscale computational studies. Rational design of lysine tweezers equipped with a peptidic recognition element thus allowed to address a previously unapproachable protein surface area. As an experimental proof-of-principle for specific transport signal interference, this concept should be transferable to any protein epitope with a flanking well-accessible lysine.},
  note = 	{<p>The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.</p>

<p>Open Access funding enabled and organized by Projekt DEAL.</p>

<p>This work was supported by the Collaborative Research Centre 1093 Supramolecular Chemistry on Proteins (T. S., P. B., D. H., S. K. K., E. S.-G.) and funded by the German Research Foundation (DFG). E. S.-G. acknowledges support from the DFG under Germany's Excellence Strategy (EXC-2033; project no. 390677874) and a{\&}{\#}xa0;Plus-3 grant from the Boehringer Ingelheim Foundation. E. S.-G. acknowledges computational time provided by the Computing and Data Facility of the Max Planck Society and the supercomputer magnitUDE of the University of Duisburg-Essen.</p>},
  note = 	{<p>Meiners, A., B{\"a}cker, S., Hadrovi{\'{c}}, I. <em>et al.</em> Specific inhibition of the Survivin--CRM1 interaction by peptide-modified molecular tweezers. <em>Nat Commun</em> <strong> 12</strong>, 1505 (2021). <a href="https://doi.org/10.1038/s41467-021-21753-9">https://doi.org/10.1038/s41467-021-21753-9</a></p>

<p>Published 08 March 2021</p>},
  note = 	{Version of Record / Verlagsversion},
  doi = 	{10.1038/s41467-021-21753-9},
  url = 	{https://duepublico2.uni-due.de/receive/duepublico_mods_00078019},
  url = 	{https://doi.org/10.1038/s41467-021-21753-9},
  file = 	{:https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00077666/Nat_Commun_2021_12_1505.pdf:PDF},
  language = 	{en}
}