A Tetraguanidinium Ligand Binds to the Surface of the Tetramerization Domain of Protein P53

A key therapeutic target in the fight against cancer, the tetramerization domain of the tumor suppressor protein P53 binds a tetraguanidinium ligand at its surface. A specific interaction involving four salt bridges was detected by two NMR-based techniques (see figure). The design of protein-surface ligands is a major challenge because of competition between the ligand and water molecules.