372 2. ANALOGS OF ENZYME REACTION COMPONENTS 



Table 2-20 {continued) 



Inhibitor 



Apparent K^ Relative — Zli^ of binding 

 (mM) (kcal/mole) 



Phenylalanine series 



Acetyl-D-phenylalaninamide 12 2 . 72 



Nicotinyl-D-phenylalaninamide 9 2.90 



Acetyl-D-phenylalanine methylester 2.3 3.74 



Benzoate 150 1.16 



Benzamide 10 2 . 83 



Phenylacetate 200 0.99 



Phenylacetamide 15 2.58 



Phenylpropionate 25 2 . 26 



Phenylpropionamide 7.0 3 . 05 



Phenylbutyrate 60 1.73 



Phenylbutyramide 12 2.72 



" The values of K^ are taken from work at pH 7.9. A", varies with the pH and thus 

 the degree of ionization may be of importance in some instances. The relative binding 

 energies are therefore subject to some error but may provide an initial basis for discus- 

 sion. Various substrates have been used in the different studies and this may introduce 

 further uncertainties. (Data from Foster et al., 1955; Foster and Niemann, 1955 a, 

 b; Lands and Niemann, 1959.) 



indole ring system. This is confirmed by comparing the phenyl and indole 

 acids and amides, the indole derivatives being bound 0.77 kcal/mole more 

 strongly on the average. 



(C) Comparing the iV-substituted Rg groups one may calculate that the 

 order of binding is: 



A = 0.35 A = 0.68 



(kcal/mole) (kcal/mole) 



Benzoyl > nicotinyl > acetyl 



and it appears that the acetyl derivatives are better inhibitors than the 

 analogs with a free NH3+ group. It is likely that these groups interact 

 with the enzyme surface in a nonspecific fashion. 



(D) Analogs with a CONH2 group are bound around 1.10 kcal/mole 

 more tightly than those with a free C00~ group. This might indicate that 

 the peptidatic site is in an electric field arising from surrounding negative 

 charges, but it could also mean that hydrogen bonds between the pep- 

 tide linkage and the enzyme are important. The rather tight binding of 



