含脲基异吲哚啉-1-酮同型-N-核苷的寡核苷酸的合成及双链DNA识别研究。主客体研究与DNA识别研究的比较。

Synthesis and duplex DNA recognition studies of oligonucleotides containing a ureido isoindolin-1-one homo-N-nucleoside. A comparison of host-guest and DNA recognition studies.

作者信息

Mertz Eric, Mattei Sebastiano, Zimmerman Steven C

机构信息

Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Matthews Avenue, Urbana, IL 61801, USA.

出版信息

Bioorg Med Chem. 2004 Mar 15;12(6):1517-26. doi: 10.1016/j.bmc.2003.12.022.

DOI:10.1016/j.bmc.2003.12.022

PMID:15018925

Abstract

In an effort to construct non-natural bases to be used in triplex-based antigene DNA recognition strategies, a uriedo-isoindolin-1-one homo-N-nucleoside base was designed to bind the cytosine-guanine (CG) base pair. An organic soluble analogue of this base was shown to effectively complex CG (K(assoc)=740M(-1)) in chloroform through formation of three hydrogen bonds (Mertz, E.; Mattei, S.; Zimmerman, S. C. Org. Lett. 2000, 2, 2931-2934). The novel nucleoside base was synthesized and successfully incorporated into oligonucleotides which were used in triple helix melting temperature studies. Low melting temperatures were observed when the isoindolin-1-one base was paired opposite CG as well as GC, TA, and AT, thus indicating that despite favorable recognition in model studies, the artificial base did not effectively recognize duplex DNA to form pyrimidine-purine-pyrimidine type triple helices.

摘要

为了构建用于基于三链体的反基因DNA识别策略的非天然碱基，设计了一种尿嘧啶异吲哚啉-1-酮同型N-核苷碱基以结合胞嘧啶-鸟嘌呤（CG）碱基对。该碱基的一种有机可溶性类似物通过形成三个氢键，在氯仿中显示出能有效络合CG（缔合常数K = 740M⁻¹）（默茨，E.；马泰，S.；齐默尔曼，S.C.《有机快报》，2000年，第2卷，2931 - 2934页）。合成了这种新型核苷碱基，并成功将其掺入用于三链螺旋解链温度研究的寡核苷酸中。当异吲哚啉-1-酮碱基与CG以及GC、TA和AT配对时，观察到解链温度较低，这表明尽管在模型研究中识别效果良好，但该人工碱基并不能有效识别双链DNA以形成嘧啶-嘌呤-嘧啶型三链螺旋。