Molecular electric field mapping and structure-activity relationships for some human O6-alkylguanine-DNA alkyl transferase depleting agents

Abstract

Electric field mapping has been carried out for certain O6- and S6-substituted purine derivatives, some of which are known to have the ability to deplete the human DNA guanine O6-alkylation damage repair enzyme called O6-alkylguanine-DNA alkyltransferase (AGT). Geometries of all the molecules are optimized using the latest semiempirical method, PM3. Point charges at different atomic sites are obtained using Mulliken population analysis. There exists a reasonably good correlation between the average electric field values near the N7 atom of the guanine moiety in these molecules and the observed AGT depleting activities. It indicates involvement of the N7 site of the guanine moiety in the reaction of these molecules with AGT, in agreement with earlier suggestions. © 1994.