SUBSTITUTED O-6-BENZYLGUANINE DERIVATIVES AND THEIR INACTIVATION OF HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE

Several new O-6-benzylguanine analogs bearing increasingly bulky subst ituent groups on the benzene ring or at position 9 were tested for the ir ability to inactivate the human DNA repair protein, O-6-alkylguanin e-DNA alkyltransferase. Substitution on the benzene ring was well tole rated although activity varied considerably with structural changes in groups attached to position 9. For this site, activity was preserved with large or small lipophilic groups while introduction of non-carboh ydrate polar groups generally reduced activity regardless of their siz e.