6-Thioguanine alters the structure and stability of duplex DNA and inhibits quadruplex DNA formation

被引：71

作者：

Marathias, VM ^{[1
]}

Sawicki, MJ ^{[1
]}

Bolton, PH ^{[1
]}

机构：

[1] Wesleyan Univ, Dept Chem, Middletown, CT 06459 USA

来源：

NUCLEIC ACIDS RESEARCH | 1999年 / 27卷 / 14期

关键词：

D O I：

10.1093/nar/27.14.2860

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The ability to chemically synthesize biomolecules has opened up the opportunity to observe changes in structure and activity that occur upon single atom substitution. In favorable cases this can provide information about the roles of individual atoms. The substitution of 6-thioguanine (6SG) for guanine is a potentially very useful single atom substitution as 6SG has optical, photocrosslinking, metal ion binding and other properties of potential utility. In addition, 6-mercaptopurine is a clinically important pro-drug that is activated by conversion into 6SG by cells. The results presented here indicate that the presence of 6SG blocks the formation of quadruplex DNA. The presence of 6SG alters the structure and lowers the thermal stability of duplex DNA, but duplex DNA can be formed in the presence of 6SG. These results indicate that some of the cytotoxic activity of 6SG may be due to disruption of the quadruplex structures formed by telomere and other DNAs. This additional mode of action is consistent with the delayed onset of cytotoxicity.

引用

页码：2860 / 2867

页数：8

共 56 条

[51] Molecular basis of genetic instability of triplet repeats [J].