423 1
J. Am. Chem. SOC.1981, 103, 4231-4239
Active-Site-Directed Inhibition of a-Chymotrypsin by Deaminatively Produced Carbonium Ions: An Example of Suicide or Enzyme-Activated-Substrate Inhibition Emil H. White,* Lynn W. Jelinski, Ieva R. Politzer, Bruce R. Branchini, and David F. Roswell Contribution from the Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21 21 8 . Received December 23, 1980
Abstract: N-Nitroso amides derived from phenylalanine and alanine were utilized as inhibitors of a-chymotrypsin, During the enzyme-catalyzed hydrolysis of these substrates, carbonium ions capable of alkylating nucleophilic groups are released in the active site. Nitroso lactams were also tested as substrates since they produce carbonium ions while still tethered to the enzyme at the acyl-enzyme stage. Kinetic studies indicated that at substrate/a-chymotrypsin ratios of 40: 1 the acyclic substrates caused the following percent inhibition of a-chymotrypsin activity (substrate, percent inhibition): D-la, 100; L-la,
