INTERACTION WITH CHOLINESTERASE 



291 



The second is considered more likely because of the stronger binding of the 

 2 — OH compared to the 4 — OH derivative; the hydroxy 1 group in the 2-po- 

 sition could form a weaker hydrogen bond with the Z group but the hydroxyl 

 in the 4-position could not. This indicates that one factor in the relative 

 binding of differently substituted derivatives is the orientation of the 

 group with respect to certain protein groups with which it may interact. 



Table 6-25 



BrS'DIXG OF PHEXYLTRIMETHYLAMMOXir.M DERIVATIVES TO ChOLIXESTERASE "^ 



" Data taken from Wilson and Quan (1958). The relative binding energies were 

 calculated with the phenyltrimethylammonium ion as the standard, and the deriv- 

 atives given, with the exception of the last two, are all of this compound. The K^?, 

 were obtained from inhibition studies on eel electric organ acetylcholinesterase. 



Introduction of further groups into the 3 — OH derivative generally 

 reduces the binding energy, pointing to steric interference with the approach 

 of the ring to the protein surface. However, the 4— CH3 — 3 — OH derivative 

 is bound more tightly than the 3 — OH derivative by 0.67 kcal/mole. Since 



