@article{HagenMattayRaeuberetal.2014,
  author    = {Hagen, Sven and Mattay, Dinah and Raeuber, Christina and Mueller, Kristian M. and Arndt, Katja Maren},
  title     = {Characterization and inhibition of AF10-mediated interaction},
  series = {Journal of peptide science},
  volume    = {20},
  journal   = {Journal of peptide science},
  number    = {6},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1075-2617},
  doi       = {10.1002/psc.2626},
  pages     = {385 -- 397},
  year      = {2014},
  abstract  = {The non-random chromosomal translocations t(10;11)(p13;q23) and t(10;11)(p13;q14-21) result in leukemogenic fusion proteins comprising the coiled coil domain of the transcription factor AF10 and the proteins MLL or CALM, respectively, and subsequently cause certain types of acute leukemia. The AF10 coiled-coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma. Using sequential synthetic peptides, we mapped the potential AF10/GAS41 interaction site, which was subsequently be used as scaffold for a library targeting the AF10 coiled-coil domain. Using phage display, we selected a peptide that binds the AF10 coiled-coil domain with higher affinity than the respective coiled-coil region of wild-type GAS41, as demonstrated by phage ELISA, CD, and PCAs. Furthermore, we were able to successfully deploy the inhibitory peptide in a mammalian cell line to lower the expression of Hoxa genes that have been described to be overexpressed in these leukemias. This work dissects molecular determinants mediating AF10-directed interactions in leukemic fusions comprising the N-terminal parts of the proteins MLL or CALM and the C-terminal coiled-coil domain of AF10. Furthermore, it outlines the first steps in recognizing and blocking the leukemia-associated AF10 interaction in histiocytic lymphoma cells and therefore, may have significant implications in future diagnostics and therapeutics. Copyright (c) 2014 European Peptide Society and John Wiley \& Sons, Ltd.},
  language  = {en}
}
@article{ZuoGandhiArndtetal.2012,
  author    = {Zuo, Zhili and Gandhi, Neha S. and Arndt, Katja Maren and Mancera, Ricardo L.},
  title     = {Free energy calculations of the interactions of c-Jun-based synthetic peptides with the c-Fos protein},
  series = {Biopolymers},
  volume    = {97},
  journal   = {Biopolymers},
  number    = {11},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0006-3525},
  doi       = {10.1002/bip.22099},
  pages     = {899 -- 909},
  year      = {2012},
  abstract  = {The c-Fosc-Jun complex forms the activator protein 1 transcription factor, a therapeutic target in the treatment of cancer. Various synthetic peptides have been designed to try to selectively disrupt the interaction between c-Fos and c-Jun at its leucine zipper domain. To evaluate the binding affinity between these synthetic peptides and c-Fos, polarizable and nonpolarizable molecular dynamics (MD) simulations were conducted, and the resulting conformations were analyzed using the molecular mechanics generalized Born surface area (MM/GBSA) method to compute free energies of binding. In contrast to empirical and semiempirical approaches, the estimation of free energies of binding using a combination of MD simulations and the MM/GBSA approach takes into account dynamical properties such as conformational changes, as well as solvation effects and hydrophobic and hydrophilic interactions. The predicted binding affinities of the series of c-Jun-based peptides targeting the c-Fos peptide show good correlation with experimental melting temperatures. This provides the basis for the rational design of peptides based on internal, van der Waals, and electrostatic interactions.},
  language  = {en}
}