Drug-Like Inhibitors Of Protein-Protein Interactions: Peptide Mimicry And Fragment Approaches
David Fry
Senior Research Leader, Hoffmann La-Roche
INHIBITING PROTEIN-PROTEIN INTERACTIONS WITH SMALL MOLECULES IS A DIFFICULT TASK, BUT COULD POTENTIALLY LEAD TO A WIDE VARIETY OF NOVEL AND IMPORTANT THERAPEUTICS. EXAMINING SUCCESS STORIES IN THIS FIELD IS USEFUL, BECAUSE COMMON THEMES AND LESSONS ARE REVEALED. THIS TALK WILL DRAW UPON EXPERIENCES WITH DRUG DISCOVERY EFFORTS ON THE P53-MDM2 SYSTEM, AS WELL AS OTHER TARGETS, TO DESCRIBE KEY FACTORS GOVERNING SUCCESS AGAINST THIS TARGET CLASS. THESE FACTORS INCLUDE THE DEPLOYMENT OF BIOPHYSICAL TECHNIQUES IN LEAD IDENTIFICATION, THE CHARACTERISTICS OF SCREENING LIBRARIES, THE SPATIAL AND CHEMICAL RELATIONSHIPS BETWEEN PEPTIDES AND SMALL ORGANIC LIGANDS, AND THE APPLICATION OF THE FRAGMENT-BASED APPROACH.
DAVID C. FRY IS CURRENTLY THE HEAD OF BIOSTRUCTURAL RESEARCH AT HOFFMANN-LA ROCHE IN NUTLEY, NJ. HIS PRIMARY INTEREST IS THE MODULATION OF PROTEIN-PROTEIN INTERACTIONS BY SMALL MOLECULES AND PEPTIDES, AND HIS INDIVIDUAL RESEARCH INVOLVES THE USE OF NMR SPECTROSCOPY FOR SCREENING AND FOR DETERMINING THE STRUCTURES OF PROTEINS AND CONSTRAINED PEPTIDES.