iPEP: peptides designed and selected for interfering with protein interaction and function.
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.
Mason
Jody M
JM
Department of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany. katja@biologie.unifreiburg.de
M Müller
Kristian
K
Arndt
Katja M
KM
D000465:Algorithms; D020816:Amino Acid Motifs; D015195:Drug Design; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D011506:Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000737:chemistry
D019151:Peptide Library; D010455:Peptides; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1