Award Address (Ronald Breslow Award for Achievement in Biomimetic Chemistry, sponsored by The Ronald Breslow Endowment). Molecular recognition in chemistry and biology

ORGN 265

François Diederich, diederich@org.chem.ethz.ch, Laboratorium für Organische Chemie, ETH Zürich, Hoenggerberg, HCI, Zürich, 8093, Switzerland
We pursue since the early 1990s a molecular recognition-based approach to medicinal chemistry. Starting from the observation of an unfamiliar intermolecular contact seen in the X-ray crystal structures of protein-ligand complexes obtained in our medicinal chemistry programs, which target malaria and other important diseases, we undertake data base mining in the Cambridge Crystallographic Database (CSD) and the Protein Data Bank (PDB) to explore the statistical relevance of the contact. If this contact is of a more general nature, we quantify it - depending on its energetic magnitude - by protein-ligand binding studies, molecular recognition studies with synthetic receptors or, if very weak, by studying intramolecular dynamic processes in designed model systems. Examples for such biomimetic systems will be presented. The application of the insight gained into biological molecular recognition phenomena to structure-based drug design will be illustrated by two recent lead developments in our programs against shigellosis and malaria.