Chomicz Lidia, Golon Łukasz, Rak Janusz
Department of Chemistry, University of Gdansk, 80-308 Gdansk, Poland.
Phys Chem Chem Phys. 2014 Sep 28;16(36):19424-8. doi: 10.1039/c4cp03139c.
Halogenated nucleotides belong to the group of radiosensitizers that sensitize solid tumors when incorporated into genomic DNA. Here, we consider the propensity of two isomeric bromocytidine derivatives, 3',5'-diphosphates of 5-bromo-2'-deoxycytidine (5BrdCDP) and 6-bromo-2'-deoxycytidine (6BrdCDP), to be damaged by electrons - one of the most abundant products formed during radiotherapy. An intranucleotide degradation mechanism leading to phosphodiester bond breakage (a model of single strand breakage in labeled DNA) and a ketone derivative formation was found for 6BrdCDP, while for 5BrdCDP a similar mechanism is sterically hindered. 5BrdCDP is, therefore, suggested to undergo electron induced degradation involving hydrogen transfer from a neighboring nucleotide or environment.
卤化核苷酸属于放射增敏剂，当它们掺入基因组DNA时可使实体瘤增敏。在此，我们研究了两种同分异构的溴胞苷衍生物，即5-溴-2'-脱氧胞苷（5BrdCDP）和6-溴-2'-脱氧胞苷（6BrdCDP）的3',5'-二磷酸酯被电子损伤的倾向，电子是放疗过程中形成的最丰富的产物之一。我们发现6BrdCDP存在一种导致磷酸二酯键断裂（标记DNA中单链断裂的模型）和形成酮衍生物的核苷酸内降解机制，而对于5BrdCDP，类似的机制在空间上受到阻碍。因此，有人提出5BrdCDP会发生电子诱导的降解，涉及从相邻核苷酸或环境中转移氢。
