370 2. ANALOGS OF ENZYME REACTION COMPONENTS 



Table 2-19 



Competitive Inhibition of a-CnYMOXRYPSiN by Analogs " 



Inhibitor 



Apparent iC, Relative — AF oi binding 



(mM) (kcal/mole) 



3-Indolepropionate 2.5 3.57 



3-Indolebutyrate 3.6 3.35 



a-Naphthylpropionate 4.0 3.28 



2,4-Dinitro-^-phenylpropionate 5.3 3.08 



^-Phenylpropionate 5.5 3.07 



2-Phenoxyethanol 5.8 3.05 



y-Phenylbutyrate 14 2.53 



Cyclohexylpropionate 30 2.08 



Cyclohexylbutyrate 35 1.99 



Benzoate 42 1.88 



Phenylacetate 42 1 . 88 



a-Naphthylmethylmalonate 55 1 . 72 



a-Benzylmalondiamide 78.8 1.51 



Cyclohexylacetate 86 1.46 



" The substrate is acetyl-L-tyrosinamide (K^ = 27 mM). Experiments at pH 7.8 

 and 25°. (Data from Neurath and Gladner, 1951.) 



For the past several years Niemann and his associates have conducted 

 excellent quantitative investigations of the inhibition of chymotrypsin 

 by a variety of analogs and their results, some of which are presented in 

 Table 2-20, provide a basis for the interpretation of the binding mechanisms. 

 Although final conclusions must await completion of their work, some tenta- 

 tive ideas may be expressed. 



(A) Despite the fact that the derivatives of L-amino acids are hydro- 

 lyzed by chymotrypsin, the D-isomers of several inhibitors are bound on an 

 average of 0.45 kcal/mole more tightly than the corresponding L-isomers 

 (see also page 271). Although three-point attachment may be important for 

 substrate binding, it is evident from this difference and other data that 

 it is not for inhibitor binding. 



{B) Comparing the derivatives of the three amino acids, it is seen that 

 the phenylalanine and tyrosine analogs are equally bound, whereas the 

 tryptophan analogs are bound some 1.19 kcal/mole more tightly, and this is 

 probably to be attributed to the greater affinity of the enzyme for the 



