Conversion of 5-iodo-2-pyrimidinone-2'-deoxyribose to 5-iodo-deoxyuridine by aldehyde oxidase. Implication in hepatotropic drug design.
Conversion of 5-iodo-2-pyrimidinone-2'-deoxyribose to 5-iodo-deoxyuridine by aldehyde oxidase. Implication in hepatotropic drug design.
复制标题
醛氧化酶将 5-碘-2-嘧啶酮-2-脱氧核糖转化为 5-碘-脱氧尿苷。
DOI：
10.1016/0006-2952(92)90186-m
复制
发表时间：
1992
影响因子：
5.8
通讯作者：
Cheng,YC
中科院分区：
文献类型：
--
作者：
Chang,CN;Doong,SL;Cheng,YC
5-碘-2-嘧啶-2'-脱氧核糖（IPdR）可通过肝脏中的醛氧化酶转化为临床放射增敏剂5-碘-脱氧尿苷（IUdR）。这种转化不需要外源辅助因子，也不能由混合功能氧化酶、黄嘌呤氧化酶或许多其他氧化还原酶催化。这种“IPdR氧化酶”活性在肝脏中丰富；因此，可以预期IPdR在肝脏广泛转化为IUdR，并且IPdR作为原发性肝癌或转移到肝脏的肿瘤的放射增敏剂的治疗指标可能优于IUdR。基于结构和活性关系的研究，可以设计出核苷类似物，这些核苷类似物可以被该酶活化成能够抑制DNA合成的化合物，并应作为抗肝癌、病毒或肝脏寄生虫的药物进行探索。
5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) can be converted into 5-iodo-deoxyuridine (IUdR), a clinical radiosensitizer, by aldehyde oxidase in the liver. This conversion does not require exogenous cofactors and cannot be catalyzed by mixed-function oxidases, xanthine oxidase or many other oxido-reductases. This “IPdR oxidase” activity is enriched in the liver; thus, extensive conversion of IPdR to IUdR could be anticipated in the liver and the therapeutic index of IPdR could be better than that of IUdR as a radiosensitizer for primary liver cancers or tumors metastasized to the liver. Based on structure and activity relationship studies, nucleoside analogues which could be activated by this enzyme to compounds capable of inhibiting DNA synthesis could be designed and should be explored as agents against cancer, viruses or parasites in the liver.