IRREVERSIBLE ENZYME INHIBITORS .148. ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF GUANINE DEAMINASE DERIVED FROM 9-PHENYLGUANINE BEARING A TERMINAL SULFONYL FLUORIDE

Thirty-eight candidate irreversible inhibitors of guanine deaminase derived from 9-phenylguanine with a terminal sulfonyl fluoride bridged lo the meta or para position of the phenyl moiety by an amide or ether linkage were evaluated with the enzyme from Walker 2.56 rat tumor. Three of the compounds (6, 7, 9) were excellent irreversible inhibitors of this enzyme, but also showed no isozyme specificity since these could also inactivate the rat liver enzyme. Of the 13 compounds showing moderate irreversible inhibition of the Walker 2.56 enzyme, four (5, 28, 30, 31) showed isozyme specificity with no inactivation of the rat. liver enzyme. © 1969, American Chemical Society. All rights reserved.