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A Carbocyclic Analog of the Oxidatively Generated DNA Lesion Spiroiminodihydantoin
Author(s) -
Müller Heiko,
Carell Thomas
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.200600982
Subject(s) - chemistry , lesion , deoxyguanosine , oligonucleotide , 8 hydroxy 2' deoxyguanosine , dna , dna oxidation , stereochemistry , dna damage , biochemistry , psychology , psychiatry
8‐Oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxo‐dG) is a mutagenic DNA lesion which is prone to further oxidation. One‐electron oxidants like Ir IV oxidize 8‐oxo‐dG to give secondary lesions such as the spiroiminodihydantoin. This lesion blocks DNA polymerases and induces G → T as well as G → C transversions. Here, we report the synthesis of a carbocyclic analog of the 8‐oxo‐dG lesion and the carbocyclic version of the spiroiminodihydantoin lesion. Both lesion analogs were obtained within single‐stranded DNA and as their corresponding nucleosides. Characterization of the lesion analogs was achieved by HPLC, ESI‐MS and ESI‐MS/MS, as well as enzymatic digestion of the oligonucleotides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)