The structural modification of DNA nucleosides by nonenzymatic glycation: an in vitro study based on the reactions of glyoxal and methylglyoxal with 2'-deoxyguanosine.
Methylglyoxal and glyoxal are generated from the oxidation of carbohydrates and lipids, and like D-glucose have been shown to nonenzymatically react with proteins to form advanced glycation end products (AGEs). AGEs can occur both in vitro and in vivo, and these compounds have been shown to exacerbate many of the long-term complications of diabetes. Earlier studies in our laboratory reported D-glucose, D-galactose, and D/L-glyceraldehyde formed AGEs with nucleosides. The objective of this study was to focus on purines and pyrimidines and to analyze these DNA nucleoside derived AGE adducts with glyoxal or methylglyoxal using a combination of analytical techniques. Studies using UV and fluorescence spectroscopy along with mass spectrometry provided for a thorough analysis of the nucleoside AGEs and demonstrated that methylglyoxal and glyoxal reacted with 2'-deoxyguanosine via the classic Amadori pathway, and did not react appreciably with 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxycytidine. Additional findings revealed that methylglyoxal was more reactive than glyoxal.
Li
Yuyuan
Y
Department of Chemistry, University of Rhode Island, Kingston, RI 02881, USA.
Cohenford
Menashi A
MA
Dutta
Udayan
U
Dain
Joel A
JA
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D004798:Enzymes / Q000378:metabolism; D006031:Glycosylation; D006037:Glyoxal / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008745:Methylation; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D013696:Temperature
D004798:Enzymes; D009705:Nucleosides; D006037:Glyoxal; D004247:DNA; D003849:Deoxyguanosine