title: Development of small molecules designed to modulate protein-protein interactions.
abstract: Protein-protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein-protein interactions is challenging, owing to the large size of protein-complex interface, the lack of well-defined binding pockets, etc. We describe a general approach based on the "privileged-structure hypothesis" [Che, Ph.D. Thesis, Washington University, 2003] - that any organic templates capable of mimicking surfaces of protein-recognition motifs are potential privileged scaffolds as protein-complex antagonists--to address the challenges inherent in the discovery of small-molecule inhibitors of protein-protein interactions.
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. chey@nhlbi.nih.gov
authors.forename: Ye
authors.initials: Y
authors.lastname: Che
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
authors.forename: Garland R
authors.initials: GR
authors.lastname: Marshall
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D011506:Proteins; D043562:Receptors, G-Protein-Coupled