Covalent modification as a strategy to block protein-protein interactions with small-molecule drugs.
It is generally difficult to block protein-protein interactions with small-molecule drugs. A novel pharmaceutical development strategy to block protein interactions is emerging: targeted covalent modification to sterically block interactions. By this approach, compounds first interact non-covalently with a specific target protein. This interaction juxtaposes a weakly reactive group of the drug with a target amino acid sidechain, which then react by virtue of their high local concentration.
Way
J C
JC
The Molecular Sciences Institute, Lexigen Pharmaceuticals, Berkeley, Lexington, CA 94704, MA 02173, USA. jway@lexigenpharm.com.
D001665:Binding Sites; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D011506:Proteins