Molecular Pharmacology, Vol 10, 954-962, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

The Quantitative Structure-Activity Relationship of 9-(X-Phenyl)-guanines Reversibly Inhibiting Guanine Deaminase: Quantitative Comparison of Enzyme from Two Sources

¹ Department of Chemistry, Pomona College, Claremont, California 91711

The structure-activity relationship for 9-(X-phenyl)guanines inhibiting guanine deaminase (EC 3.5.4.3) has been studied using substituent constants and regression analysis. The resulting quantitative relationship confirms what one might expect a priori: there are two types of space in or on an enzyme with which substituents might interact. Substituents in position 4 of the phenyl ring interact with hydrophobic space, while substituents in position 3 interact with polar space. The electronic effects of substituents on the phenyl ring appear to be of very minor importance. Steric effects of 2-functions are quite important. Equations were formulated for enzymes from two sources: rabbit liver and Walker 256 rat tumor. While different sets of congeners were studied with the two different enzymes, similar equations were obtained, showing the great similarity in enzyme from two different sources.