Premium
Reactivity of the Malonaldehyde‐Glyoxal and Malonaldehyde‐Methylglyoxal Adducts of Adenine Nucleosides toward Amino Acid Cross‐Link Formation
Author(s) -
PluskotaKarwatka Donata,
Matysiak Dorota,
Makarewicz Marta,
Kronberg Leif
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200436
Subject(s) - methylglyoxal , chemistry , glyoxal , electrophile , adduct , deoxyadenosine , lysine , stereochemistry , reactivity (psychology) , nucleobase , nitrosation , purine , ribose , dna , biochemistry , amino acid , organic chemistry , enzyme , medicine , alternative medicine , pathology , catalysis
DNA–protein cross‐links are formed upon exposure to a variety of physical and exogenous, as well as endogenous chemical agents. This type of damage poses a threat to genomic integrity. Among the agents capable of inducing DNA–protein cross‐links bifunctional electrophiles arising from cellular processes deserve particular attention. Representatives of such electrophiles include glyoxal, methylglyoxal and malonaldehyde. Herein, we report that glyoxal and methylglyoxal adducts of 2′‐deoxyadenosine formed in the presence of malonaldehyde {M 1 Gx‐dA [8‐(diformylmethyl)‐3‐(2′‐deoxy‐β‐ D ‐ribofuranosyl)imidazo[2,1‐ i ]purine], and M 1 MGx‐dA [8‐(diformylmethyl)‐7‐methyl‐3‐(2′‐deoxy‐β‐ D ‐ribofuranosyl)imidazo[2,1‐ i ]purine], respectively}, display high reactivity towards lysine derivatives. In reactions with N α ‐acetyllysine M 1 Gx‐dA was found to form three adducts whereas M 1 MGx‐dA reacted with the lysine congener to form two stable products. All compounds were isolated and their structures determined on the basis of 2D NMR spectroscopy. Formation of the analogous products was shown in the individual reactions of M 1 Gx‐dA and M 1 MGx‐dA with N ϵ ‐acetyllysine. Mechanisms proposed for formation of all characterised compounds are also discussed. This study reports identification of structures for a potentially new class of DNA–protein cross‐links.