368 2. ANALOGS OF ENZYME REACTION COMPONENTS 



example, L-leucine, D-alanine, and glycine inhibit the hydrolysis of alanyl- 

 glycine and glycylglycine (Grassmann et al., 1935). This has been investi- 

 gated more quantitatively by Nishi (1960) and his results are summarized 

 in the accompanying tabulation (substrate is glycylglycine at 50 mM). 

 These inhibitions are competitive with respect to substrate and uncompe- 

 titive with respect to Co++. Some interesting inhibitions of pig kidney 

 leucine aminopeptidase have been reported by Hill and Smith (1957). 

 The hydrolysis of substrates of the type R— CH(NH3+)— CONH— R' 

 depends on a three-point attachment of the R group, the NH3+ group, 

 and the amide N. The R groups interact by van der Waals' forces; further 

 energy is contributed from the hydrogen bonding of water molecules dis- 

 placed from the hydrophobic surfaces. The inhibitions given in the follow- 

 ing tabulation are for L-leucinamide as substrate at 50 mM and at pH 8.50- 



8.65. Every good inhibitor contains an R group that should give nearly 

 optimal interaction with the electrokinetic site of the enzyme; in addition, 

 at least one group that will react with the bound Mn++ is present. 



CHYMOTRYPSIN AND OTHER PROTEOLYTIC ENZYMES 



Chymotrypsin hydrolyzes various amides and esters of the general type: 



NH— R2 

 Rj — CH2 CH 



bo— R3 



where R^ represents the side chains of amino acids (phenylalanine, tyrosine, 

 and tryptophan most commonly used), Rg is an acyl group (acetyl, benzoyl, 



