CRC 1093 - Project B5
Biological Targets B5: Rational targeting of intracellular protein transport signals by supramolecular ligands
Applied supramolecular chemistry harbors an enormous potential, not only for understanding protein function but also to elucidate pathomechanisms in human diseases. We expect here to demonstrate that supramolecular ligands can indeed be developed and applied to rationally target nucleo-cytoplasmic transport signals, such as the NES of Survivin (SP1) and the NLS of Taspase1 (SP2). As outlined before, the obtained results will aid to improve our understanding of the biological functions of Survivin and Taspase1, and pave the way to a hypothesis-driven inhibitor design for these onco- logically relevant proteins. Moreover, we follow up on our first experimental proof-of-principle that specific binding to intracellular transport signals can indeed be achieved by supramolecular ligands, and transfer this strategy from nuclear export to import signals. As also the activity of several disease-driving proteins is based on selective nuclear transport and protein interactions, the results are expected to set the stage for the future exploitation of the developed principles in basic and applied biomedical research.