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1 H‐ und 13 C‐NMR‐Konformationsanalysen und Minimal‐Potential‐Energie‐Rechnungen an Desoxyguanosin‐, Guanosin‐ und 5′‐Guanosinmonophosphat‐Addukten des Grenzcarcinogens 4‐Methylanilin
Author(s) -
Meier Chris,
Boche Gernot
Publication year - 1990
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19901230821
Subject(s) - chemistry , adduct , deoxyguanosine , stereochemistry , guanosine , nuclear magnetic resonance spectroscopy , nucleotide , glycosidic bond , dna adduct , biochemistry , enzyme , organic chemistry , gene
The conformations of the C‐8‐nucleobase adducts of the borderline carcinogen 4‐methylaniline ( p ‐toluidine) N ‐(deoxyguanosine‐8‐yl)‐4‐methylaniline ( 10 ), N ‐(guanosine‐8‐yl)‐4‐methylaniline ( 11 ), and 8‐(4‐methylanilino)‐5′‐guanosinemonophosphate ( 12 ) have been investigated by 1 H‐, 13 C‐NMR spectroscopy and “minimal‐potential‐energy” calculations. As far as the glycosidic bond is concerned, the 1 H‐ and 13 C‐NMR data show in agreement with the calculations that the nucleoside adducts 10, 11 exist preferentially in the anti conformation while the 5′‐phosphorylated nucleotide adduct 12 exists in the syn conformation. Different conformations are also observed around the backbone C‐4′ – C‐5′ bond. While the nucleoside adducts 10, 11 show a strong preference for the gauche‐gauche conformation (ca. 90%), nucleotide adduct 12 exists mainly in the gauche‐trans/trans‐gauche conformation (ca. 70%). All adducts show a preference for the C‐2′‐ endo conformation of the (deoxy)ribose puckering. A comparison of the conformational data of monocyclic arylamine adducts 10, 11 , and 12 with the conformations of DNA‐ or oligonucleotide‐bonded 2‐[(deoxyguanosine‐8‐yl)amino]fluorene ( 6 ) shows, that the conformational situations in the case of the borderline carcinogen p ‐toluidine are similar to that of the strong hepatocarcinogen 2‐aminofluoren ( 4b ). The reasons for the different cancer‐inducing potentials of borderline carcinogens like p ‐toluidine and strong carcinogens like 2‐aminofluorene thus seems not to be connected with the conformational changes of the DNA double helix caused by adduct formation but rather with the in vivo metabolization to give the ultimate carcinogen.