Substitution of aminomethyl at the meta-position enhances the Inactivation of O 6-alkylguanine-DNA alkyltransferase by O 6-benzylguanine

…, NA Loktionova, Q Fang, SL Vankayala…

Index: Pauly, Gary T.; Loktionova, Natalia A.; Fang, Qingming; Vankayala, Sai Lakshmana; Guida, Wayne C.; Pegg, Anthony E. Journal of Medicinal Chemistry, 2008 , vol. 51, # 22 p. 7144 - 7153

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Citation Number: 18

Abstract

O 6-Benzylguanine is an irreversible inactivator of O 6-alkylguanine-DNA alkyltransferase currently in clinical trials to overcome alkyltransferase-mediated resistance to certain cancer chemotherapeutic alkylating agents. In order to produce more soluble alkyltransferase inhibitors, we have synthesized three aminomethyl-substituted O 6-benzylguanines and the three methyl analogs and found that the substitution of aminomethyl at the meta-position ...

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