Interfering Peptides Targeting Protein-Protein Interactions

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March 19, 2015

Protein-protein interaction surfaces are attractive yet challenging targets for disease intervention. We present strategies to combine rational design with in-vivo and in-vitro selection systems and implementing competitive and negative design aspects to simultaneously select for affinity and specificity. Using such a semi-rational evolutionary approach, we generated interfering peptides (iPEP) specifically directed against the coiled-coil interaction motif as found in transcription factors such as Jun, Fos, AF10 and MITF. Modifications such as photo-switchable iPEPs for external control of inhibitor activity and D-peptides for protease resistance will be discussed as well. Specific targeting of tumor cells and efficient cellular delivery has been implemented by a modular virus system based on the adeno-associated virus.

Drug Discovery

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