Chemical Modification of the Third Strand: Differential Effects on Purine and Pyrimidine Triple Helix Formation
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- 作者：Martin Mills ; Paola B. Arimondo ; Laurent Lacroix ; Thé ; rè ; se Garestier ; Horst Klump ; and Jean-Louis Mergny
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：January 8, 2002
- 年：2002
- 卷：41
- 期：1
- 页码：357 - 366
- 全文大小：161K
- 年卷期：v.41,no.1(January 8, 2002)
- ISSN：1520-4995
文摘
DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of geneexpression. Oligonucleotide analogues are routinely used with modifications in either the backbone orthe bases to form more stable triple-helical structures or to prevent their degradation in cells. In thisarticle, different chemical modifications are tested in a model system, which sets up a competition betweenthe purine and pyrimidine motifs. For most modifications, the 
H
of purine triplex formation is close tozero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex isstrongly favored at lower temperatures. The stabilization induced by modifications previously known tobe favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GTmotif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands competefor triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed atneutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on thechemical nature of the triplex-forming strands and the stability of the corresponding triplexes.
H of purine triplex formation is close tozero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex isstrongly favored at lower temperatures. The stabilization induced by modifications previously known tobe favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GTmotif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands competefor triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed atneutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on thechemical nature of the triplex-forming strands and the stability of the corresponding triplexes.