Reaction of glycidamide with 2'-deoxyadenosine and 2'-deoxyguanosine--mechanism for the amide hydrolysis.
2'-Deoxyadenosine (dA) and 2'-deoxyguanosine (dG) were reacted with 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) (Scheme 2). 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.
Backman
Josefin
J
Laboratory of Organic Chemistry, Abo Akademi University, Turku/Abo, Finland.
Kronberg
Leif
L
D000577:Amides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003839:Deoxyadenosines / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
D000577:Amides; D003839:Deoxyadenosines; D004852:Epoxy Compounds; C071834:glycidamide; D003849:Deoxyguanosine; C058118:2'-deoxyadenosine