New fragment-based drug design technology by NMR spectroscopy

This application is for the development of a new approach of fragment-based drug design, using innovative nuclear magnetic resonance (NMR) techniques for structural analysis of the bound compounds. The approach relies on NMR analysis of the pseudocontact chemical shifts induced by paramagnetic lanthanides that are attached to the target protein at different sites. It is designed to work in solution and deliver structure information even for weakly binding compounds. In addition, a strategy for the assignment of NMR signals of >100 kDa proteins will be developed and cell-free protein synthesis techniques will be devised for the production of isotope-labelled peptides and for site-specific lanthanide-labelling using an unnatural amino acid.