HOW TO KEEP PROTEINS APART

Abstract

USING SMALL MOLECULES TO prevent protein-protein interactions is like using tiny spheres to separate the strands of cooked spaghetti. It generally doesn't work. But what if the small molecule recruits another protein to give it some bulk? That strategy works beautifully, according to Jason E. Gestwicki, Gerald R. Crabtree, and Isabella A. Graef at Stanford University Medical School. They have shown that a molecule with one part that binds tightly to a helper protein and another part that interacts with â-amyloid peptide prevents aggregation of the peptide into fibrils [ Science , 306 ,865(2004)}. The formation of s-amyloid peptide fibrils is a key target in drug development for Alzheimer's disease. For decades, pharmaceutical companies have been looking for ways to prevent that aggregation, Crabtree says. But small molecules do not have enough steric bulk. So the Stanford team borrowed the surface area of another protein to help form a barrier between s-amyloid peptides. The strategy is ingenious, says ...