Abstract：
:Methylglyoxal is a mutagenic bis-electrophile that is produced endogenously from carbohydrate precursors. Methylglyoxal has been reported to induce DNA-protein cross-links (DPCs) in vitro and in cultured cells. Previous work suggests that these cross-links are formed between guanine and either lysine or cysteine side chains. However, the chemical nature of the methylglyoxal induced DPC have not been determined. We have examined the reaction of methylglyoxal, deoxyguanosine (dGuo), and Nα-acetyllysine (AcLys) and determined the structure of the cross-link to be the N2-ethyl-1-carboxamide with the lysine side chain amino group (1). The cross-link was identified by mass spectrometry and the structure confirmed by comparison to a synthetic sample. Further, the cross-link between methylglyoxal, dGuo, and a peptide (AcAVAGKAGAR) was also characterized. The mechanism of cross-link formation is likely to involve an Amadori rearrangement.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Petrova KV,Millsap AD,Stec DF,Rizzo CJdoi
10.1021/tx500068vsubject
Has Abstractpub_date
2014-06-16 00:00:00pages
1019-29issue
6eissn
0893-228Xissn
1520-5010journal_volume
27pub_type
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