Solving the problem of shape-shifters
Investigators at Harvard-affiliated Massachusetts General Hospital (MGH) may have found a way to solve a problem that has plagued ligand-mimicking integrin inhibitors, a group of drugs that have the potential to treat conditions ranging from heart attacks to cancer metastasis. In a Nature Structural & Molecular Biology paper receiving advance online publication, the researchers provide a structural basis for the design of new and safer integrin inhibitors. Integrins are receptor proteins found on the surface of cells, and they determine whether cells adhere to adjacent cells and the surrounding extracellular matrix. Under normal circumstances, integrins only become activated — which allows them to bind to other cells or extracellular molecules — in response to specific signals from within the cell. If integrins become overactive, cells become too “sticky,” leading to clogged arteries, pathological inflammation, the excess tissue growth called fibrosis, or the spread of cancer. Current drugs developed to inhibit integrin activation by mimicking the...