Peptide-protein interactions as probed by NMR with living cell

NMR spectroscopy has been widely employed to characterize molecular interactions between biomacromolecules and their ligands at different levels of complexity. Access to the fine structural details of recognition processes is essential for understanding fundamental mechanisms underlying phenomena of biological and biomedical relevance. Looking at the interaction phenomena from the ligand's perspective, STD and trNOESY are the most robust and versatile NMR techniques.[1] These experiments make it possible to study molecular recognition events involving membrane receptors and their ligands by using samples that contained platelets or whole cells and exploiting liquid state NMR spectroscopy. In light of these considerations, we used NMR methodologies to investigate the interaction between a potent VEGF agonist peptide [2, 3] and membrane-bound VEGF receptors either in vitro and in living PAE cells. This approach provides key information about the ligand's binding mode in the natural environment and allows us to propose a potential functional mechanism. These results will facilitate the design of novel VEGF agonist and establish the conditions for the NMR studies of the receptor-bound conformations of other VEGF mimicking peptides.