TRIPLER FORMATION AT THE RAT NEU GENE UTILIZING IMIDAZOLE AND 2'-DEOXY-6-THIOGUANOSINE BASE SUBSTITUTIONS

被引:38
作者
GEE, JE
REVANKAR, GR
RAO, TS
HOGAN, ME
机构
[1] BAYLOR COLL MED, CTR BIOTECHNOL, THE WOODLANDS, TX 77381 USA
[2] TRIPLEX PHARMACEUT CORP, THE WOODLANDS, TX 77380 USA
关键词
D O I
10.1021/bi00006a026
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
Triplex-forming oligodeoxyribonucleotides (TFOs) can be designed so as to form antiparallel triple helices with duplex DNA by means of GGC and TAT or AAT base triplets, and these have been shown to be useful as sequence-specific DNA binding agents. Using TFOs targeted to the promoter region of the rat neu oncogene, it is shown here that substitution of an imidazole-nucleoside chimera at a single site in a neu specific TFO results in an increase in TFO binding affinity and specificity. This effect is discussed in terms of the stabilizing effect of local imidazole-TA triplet formation. It is also found that site-selective substitution of 2'-deoxy-6-thioguanosine for guanosine (S6-dG) in the TFO results in an increase in triplex formation in the presence of physiological levels of potassium ion. The utility and positioning of S6-dG base substitutions is discussed in the context of an intramolecular tetrad model.
引用
收藏
页码:2042 / 2048
页数:7
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