| TECHNOLOGY |
different approach to find small-molecule inhibitors of kinases. Kinases act by transferring a phosphate group from adenosine triphosphate (ATP) to another molecule. But because all kinases use ATP as a substrate, finding small molecules that act on specific kinases is extremely difficult.
To get around this problem, author starts with a promiscuous molecule known to inhibit many different kinases by binding in the active site. He then alters the active site of the targeted kinase to make its ATP binding site big enough to accommodate a bulkier version of the original inhibitor. This mutated kinase is perfectly functional but uniquely able to bind the modified inhibitor. When the modified inhibitor is introduced into cells in which its engineered-kinase binding partner has been substituted for the native kinase, only the engineered kinase is inhibited. Authors have used the technique to create specific inhibitors for more than 20 different kinases. These inhibitors allow specific kinases to be selectively and rapidly disabled in order to gain functional information about their role in signaling
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