The serine hydrolases constitute a large class of enzymes that play important roles in physiology. There is great interest in the development of potent and selective pharmacological inhibitors of these proteins. Traditional active-site inhibitors often have limited selectivity within this superfamily and are tedious and expensive to discover. Using the serine hydrolase RBBP9 as a model target, we designed a rapid and relatively inexpensive route to highly selective peptoid-based inhibitors that can be activated by visible light. This technology provides rapid access to photo-activated tool compounds capable of selectively blocking the function of particular serine hydrolases.
Liu X, Dix M, Speers AE, Bachovchin DA, Zuhl AM, Cravatt BF, Kodadek TJ (2012) Rapid development of a potent photo-triggered inhibitor of the serine hydrolase RBBP9 Chembiochem13: 2082-93
Liu X, Dix M, Speers AE, Bachovchin DA, Zuhl AM, Cravatt BF, Kodadek TJ (2012) Chembiochem13: 2082-93