Durland R H, Rao T S, Bodepudi V, Seth D M, Jayaraman K, Revankar G R
Triplex Pharmaceutical Corporation, The Woodlands, TX 77380.
Nucleic Acids Res. 1995 Feb 25;23(4):647-53. doi: 10.1093/nar/23.4.647.
The ability of certain azole substituted oligodeoxy-ribonucleotides to promote antiparallel triple helix formation with duplex targets having CG or TA interruptions in the otherwise homopurine sequence was examined. 2'-Deoxyribonucleosides of the azoles, which include pyrazole, imidazole, 1,2,4-triazole and 1,2,3,4-tetrazole were synthesized using the stereo-specific sodium salt glycosylation procedure. These nucleosides were successfully incorporated using solid-support, phosphoramidite chemistry, into oligonucleotides designed to interact with the non-homopurine duplex targets. The interaction of these modified oligonucleotides with all four possible base pairs was evaluated and compared to similar data for a series of natural oligonucleotides. The oligonucleotides containing simple azoles enhanced the triplex forming ability considerably at non-homopurine targets. Binding of these modified oligonucleotides to duplex targets containing TA inversion sites was particularly noteworthy, and compare favorably to unmodified oligonucleotides for binding to duplex targets containing CG as well as TA base pairs. The selectivity exhibited by certain azoles is suggestive of base pair specific interactions. Thus, the azoles evaluated during this study show considerable promise for efforts to develop generalized triplex formation at non-homopurine duplex sequences.
研究了某些唑取代的寡脱氧核糖核苷酸与在其他方面为同型嘌呤序列中具有CG或TA间断的双链靶标促进反平行三链螺旋形成的能力。使用立体特异性钠盐糖基化方法合成了包括吡唑、咪唑、1,2,4-三唑和1,2,3,4-四唑在内的唑的2'-脱氧核糖核苷。这些核苷使用固相亚磷酰胺化学方法成功掺入到设计用于与非同型嘌呤双链靶标相互作用的寡核苷酸中。评估了这些修饰的寡核苷酸与所有四种可能碱基对的相互作用，并与一系列天然寡核苷酸的类似数据进行了比较。含有简单唑的寡核苷酸在非同型嘌呤靶标处显著增强了三链形成能力。这些修饰的寡核苷酸与含有TA倒位位点的双链靶标的结合特别值得注意，并且与未修饰的寡核苷酸相比，在与含有CG以及TA碱基对的双链靶标的结合方面表现良好。某些唑表现出的选择性暗示了碱基对特异性相互作用。因此，在本研究中评估的唑对于在非同型嘌呤双链序列中开发通用的三链形成的努力显示出相当大的前景。
