%0 Journal Article %A Ellis, David A. %A Wolkenberg, Scott E. %A Boger, Dale L. %D 2001 %T Metal Cation Complexation and Activation of Reversed CPyI Analogues of CC-1065 and Duocarmycin SA:  Partitioning the Effects of Binding and Catalysis %U https://acs.figshare.com/articles/journal_contribution/Metal_Cation_Complexation_and_Activation_of_Reversed_CPyI_Analogues_of_CC-1065_and_Duocarmycin_SA_Partitioning_the_Effects_of_Binding_and_Catalysis/3634443 %R 10.1021/ja010769r.s001 %2 https://acs.figshare.com/ndownloader/files/5723193 %K DNA alkylation %K CPyI analogues %K alkylation subunit %K Reversed CPyI Analogues %K enantiomeric selectivity %K metal cation activation %K DNA alkylating agents %K DNA alkylation rate %K CC %K novel class %K noncovalent binding selectivity %K metal Cation Complexation %K SA %K DNA binding affinity %K DNA alkylation selectivity %X The synthesis and examination of a novel class of reversed CPyI analogues of CC-1065 and the duocarmycins are described. Capable of a unique metal cation activation of DNA alkylation, these agents allowed the effects of the DNA binding domain (104-fold increase in DNA alkylation rate and efficiency) to be partitioned into two components:  that derived from enhanced DNA binding affinity and selectivity (10−80-fold) and that derived from a contribution to catalysis (250−5000-fold). In addition, the reversed enantiomeric selectivity of these sequence selective DNA alkylating agents provides further strong support for a previously disclosed model where it is the noncovalent binding selectivity of the compounds, and not the alkylation subunit or the source of catalysis, that controls the DNA alkylation selectivity. %I ACS Publications