Journal
BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 36, Issue -, Pages 1442-1447Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BST0361442
Keywords
activator protein-1 (AP-1); basic leucine zipper (bZIP); interfering peptide; protein-fragment compleentation assay (PCA); protein-protein interaction; semi-rational design
Categories
Funding
- DFG [373/1-1, 1-2]
- Cameras Leukemia Foundation [R 06/12]
- Excellence Institute of the German Federal and State Governments
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Semi-rational design is combined with PCAs (protein-fragment complementation assays) and phage-display screening techniques to generate a range of iPEPs (interfering peptides) that target therapeutically relevant proteins with much higher interaction stability than their native complexes. PCA selection has been improved to impose a competitive and negative design initiative on the library screen, thus simultaneously improving the specificity of assay 'winners'. The folding pathways of designed pairs imply that early events are dominated by hydrophobic collapse and helix formation, whereas later events account for the consolidation of more intricate intermolecular electrostatic interactions.
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