Abstract
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.
- Copyright ©, 1974, by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|