Reaction of glycidamide with 2′-deoxyadenosine and 2′-deoxyguanosine - Mechanism for the amide hydrolysis

Article abstract of DOI:10.1080/15257770601112697

2′-Deoxyadenosine (dA) and 2′-deoxyguanosine (dG) were reacted with the mutagenic epoxide glycidamide (GA, Scheme 1). The reactions yielded three GA-dA adducts (N1-GA-dA, N⁶-GA-dA and N1-GA-dI) and two GA-dG adducts (N1-GA-dG I and N1-GA-dG II) (). The structures of the adducts were characterized by spectroscopic and spectrometric methods (¹H-, ¹³C, and 2D NMR, MS, UV). The mechanism of the amide hydrolysis taking place during formation of the adducts N1-GA-dA and N1-GA-dG I was studied. We propose a mechanism where a transamidation is the key step in the hydrolysis of the amide function of GA. Copyright Taylor & Francis Group, LLC.