血吸虫杀虫剂海恩酮的作用方式：DNA烷基化位点。

Mode of action of the schistosomicide hycanthone: site of DNA alkylation.

作者信息

Archer S, el-Hamouly W, Seyed-Mozaffari A, Butler R H, Pica-Mattoccia L, Cioli D

机构信息

Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12180-3590.

出版信息

Mol Biochem Parasitol. 1990 Nov;43(1):89-95. doi: 10.1016/0166-6851(90)90133-7.

DOI:10.1016/0166-6851(90)90133-7

PMID:2290447

Abstract

Condensation of hycanthone N-methylcarbamate (HNMC) with deoxyguanosine (dG) furnished a mixture of the N-1 and N2 adducts which were purified and characterized as their acetates. Condensation of HNMC with thymidine (T) gave the N-3 adduct in poor yield. Adenosine (A) and cytidine (C) did not react with HNMC. Incubation of schistosomes with either [3H]hycanthone (HC) or [3H]HNMC furnished DNA to which [3H]HC was covalently bound. The alkylated DNA was degraded enzymically and the radiolabeled nucleosides were separated using HPLC. Two major peaks were observed which coincided in retention time with the synthetic N-1 and N2 alkylated dG. Alkylated T was absent. Thus, the site of alkylation of DNA by either HC or HNMC is dG.

摘要

海恩酮N-甲基氨基甲酸酯（HNMC）与脱氧鸟苷（dG）缩合得到N-1和N2加合物的混合物，将其纯化并表征为它们的乙酸酯。HNMC与胸苷（T）缩合得到产率较低的N-3加合物。腺苷（A）和胞苷（C）不与HNMC反应。用[3H]海恩酮（HC）或[3H]HNMC孵育血吸虫，得到与[3H]HC共价结合的DNA。将烷基化的DNA进行酶促降解，并使用高效液相色谱法分离放射性标记的核苷。观察到两个主要峰，其保留时间与合成的N-1和N2烷基化dG一致。未检测到烷基化的T。因此，HC或HNMC对DNA的烷基化位点是dG。