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Journal of Peptide Science J. Pept. Sci. (2008)
 

Summary: Journal of Peptide Science
J. Pept. Sci. (2008)
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/psc.1038
Targeting the c-Myc coiled coil with interfering peptides
EVA M. JOUAUX, KARIN SCHMIDTKUNZ, KRISTIAN M. M¨ULLER and KATJA M. ARNDT*
Institute for Biology III, Albert-Ludwigs University of Freiburg, Schaenzlestr. 1, D-79104 Freiburg, Germany
Received 20 November 2007; Revised 22 January 2008; Accepted 27 February 2008
Abstract: c-Myc is one of the most frequently deregulated oncogenes in human cancers, and recent studies showed that even
brief inactivation of Myc can be sufficient to induce tumor regression or loss. Consequently, inactivation of Myc provides a novel
therapeutic opportunity and challenge, as the dimerization of Myc with Max is crucial for its function. We applied two strategies to
specifically target this coiled coil mediated interaction with interfering peptides: a dominant-negative human Max sequence (Max)
and a peptide selected from a genetic library (Mip). Both peptides form coiled coils and were fused to an acidic extension interacting
with the basic DNA-binding region of human Myc. The genetic library was obtained by semi-rational design randomizing residues
important for interaction, and selection was carried out using a protein-fragment complementation assay. The peptides Max and
Mip easily outcompeted the human Myc : Max interaction and successfully interfered with the DNA binding of the complex. Both
interfering peptides exhibited higher Tm ( Tm = 13 and 15 °C) upon interaction with Myc compared to wt Max. The inhibitory
effect of the two interfering peptides on human Myc : Max activity makes them promising molecules for analytical and therapeutic
Myc-directed research. Copyright 2008 European Peptide Society and John Wiley & Sons, Ltd.
Keywords: Myc; Max; coiled coil; leucine zipper; rational design; library selection; dominant-negative; protein-fragment
complementation assay

  

Source: Arndt, Katja - Institut für Biologie III, Albert-Ludwigs-Universität Freiburg

 

Collections: Biotechnology; Biology and Medicine