Reaction of Glycidamide with 2′-Deoxyadenosine and 2′-Deoxyguanosine—Mechanism for the Amide Hydrolysis

Abstract

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) (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.

Keywords:

• Glycidamide
• nucleosides
• adducts
• amide hydrolysis

This work was a part of the EU-project “Heat-generated food-toxicants, identification, characterisation and risk minimisation” and was financed by the European Commission under Contract No. FOOD-CT-2003–506820 (STREP). This work was also financed by the Foundation of Magnus Ehrnrooth and the Foundation of the Research Institute at Åbo Akademi University.

Notes

^aSeparate shifts due to mixture of diastereomers.

^bSignal overlapped by solvent.

^aSignal overlapped by C-3′.

^aSeparate shifts due to mixture of diastereomers.

^bSignal overlapped by H-5′.

^cSignal overlapped by solvent.

^aSignal overlapped by solvent.

^bCarbon signal from the HSQC spectrum.

^cSeparate shifts due to mixture of diastereomers.

^aAll carbon chemical shifts are based on C-H correlations, due to insufficient sample amount for recording a ¹³C spectrum.

^bSeparate shifts due to mixture of diastereomers.