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Identification of Adducts Formed in the Reactions of 2′‐Deoxyguanosine and Calf Thymus DNA with Glutaraldehyde
Author(s) -
Olsen Raymond,
Backman Josefin,
Molander Paal,
Klika Karel D.,
Kronberg Leif
Publication year - 2007
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.200700251
Subject(s) - chemistry , adduct , deoxyadenosine , deoxyguanosine , diastereomer , glutaraldehyde , stereochemistry , depurination , dna , organic chemistry , biochemistry
Glutaraldehyde (1,5‐pentanedial) is a widely used industrial chemical that has been found to be mutagenic in bacteria and mammalian cells. It has been claimed that glutaraldehyde forms adducts with 2′‐deoxyguanosine, 2′‐deoxyadenosine and 2′‐deoxycytidine, but until recently none of the adducts had been identified. In a very recent contribution from our laboratories, the structures were determined of three glutaraldehyde adducts formed in the reaction with 2′‐deoxyadenosine, and it was shown that one of the adducts is formed in calf thymus DNA. In the current work, we have studied the reaction of glutaraldehyde with 2′‐deoxyguanosine and calf thymus DNA in aqueous buffered solutions. Among the numerous adducts formed in the reaction with 2′‐deoxyguanosine, six compounds were found to be stable and could be isolated by semi‐preparative liquid chromatography and identified by UV absorbance and 1 H and 13 C NMR spectroscopic and mass spectrometric studies. Adduct dG350b , comprising two diastereomers, was found to be derived from one unit of glutaraldehyde which has been transformed to a tetrahydropyran ring so that C‐2 and C‐6 of the ring are attached to N‐1 and N 2 of the purine unit resulting in a bridged structure. The adducts dG349a and b are analogous to dG350b , but the oxygen atom in the bridgehead position has been replaced by a nitrogen atom resulting in a piperidine ring. Adducts dG349a and b bear a diastereomeric relationship to one another and were not only separable, but were configurationally assigned. Adduct dG599 , also comprising two diastereomers, is similar to dG349a and b , but the nitrogen atom in the piperidine ring in this case is the exocyclic amino nitrogen atom of another 2′‐deoxyguanosine unit. It was found that adducts dG350b and dG349a and b were formed in calf thymus DNA. Plausible mechanisms for the formation of these adducts are presented.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)