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3 H‐labelled alkyl‐nucleotides, ‐nucleosides and ‐bases for the immunoanalytical quantification of DNA damage and repair
Author(s) -
Drosdziok Wolfgang,
Lutze Catrin,
Krüger Kai,
Glüsenkamp KarlHeinz,
Rajewsky Manfred F.
Publication year - 2003
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.721
Subject(s) - chemistry , guanine , thymidine , guanosine , thymine , alkyl , alkylation , dna , stereochemistry , deoxyguanosine , nucleotide , deoxyribonucleoside , cytosine , nucleoside , biochemistry , organic chemistry , gene , catalysis
Analysis of the formation and repair of structurally modified DNA is of particular interest in the study of carcinogenesis, cancer therapy and aging. The quantification of specific DNA lesions by sensitive immunoanalytical methods requires radiotracers with high specific activity. We describe the synthesis of 3 H‐labelled adenine‐, cytosine‐, guanine‐ and thymine‐alkyl derivatives by nucleophilic N ‐ and O‐ alkylation using alkyl halides and diazoalkanes: 3‐alkyl‐[8‐ 3 H]adenine (Alkyl = Me, Et, n‐ Bu); O 6 ‐alkyl‐deoxy[1′,2′‐ 3 H]guanosine (Alkyl = Me, Et, i ‐Pro, n ‐Bu); O 6 ‐ethyl‐deoxyguanosine‐5′‐triphosphate ([2‐ 3 H‐Ethyl]; [8‐ 3 H]); O 6 ‐alkyl‐9‐hydroxyhexyl‐[8‐ 3 H] guanine (Alkyl=Me, Et); 7‐ethyl‐[8,5′‐ 3 H]guanosine‐3′,5′‐cyclic‐phosphate; O 2 ‐and O 4 ‐alkyl‐[methyl, 1′,2′‐ 3 H]thymidine (Alkyl=Me, Et); the conversion of 3 H‐labelled thymidine to the corresponding 5‐methylcytidine; the synthesis of three different 8‐oxo‐guanine tracers; and the generation of thymidine glycol (5,6‐dihydroxy‐5,6‐dihydro‐[methyl‐ 3 H]thymidine) from thymidine. All radiotracers were sucessfully employed in competitive radioimmunoassays for the quantification of defined DNA alkylation products in DNA repair analyses. Copyright © 2003 John Wiley & Sons, Ltd.