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首页> 外文期刊>Angewandte Chemie >DNA-Carbohydrate Recognition: Design and Synthesis of an Eight-Base Sequence-Selective DNA-Binding Oligosaccharide
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DNA-Carbohydrate Recognition: Design and Synthesis of an Eight-Base Sequence-Selective DNA-Binding Oligosaccharide

机译：DNA碳水化合物识别：八碱基序列选择性DNA结合寡糖的设计与合成。

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DNA-binding molecules, particularly those with sequence specificity, have considerable potential in chemistry, biology, and medicine. Such molecules may provide the basis for further insights in the chemistry and structure of DNA. for the design and development of tools for molecular and cell biology, and for the development of antisense and gene therapies. Following calicheamicin 7_1~I as a lead, we have recently synthesized and studied the binding of a series of oligosaccharides to duplex DNA. In these investigations oligosaccharide 1 (Scheme 1) emerged as the most potent and selective molecule, binding duplex DNA at TCCT sites with an affinity constant of K_aapprox=10~6M~(-1). First synthesized in 1990 in our laboratory. oligosaccharide 1 was recently shown by Crabtree.et al. to specifically inhibit transcription complexes. Appropriately designed oligomers of 1 should exhibit enhanced binding to duplex DNA in terms of potency and specificity. We now wish to report the design and chemical synthesis of the head-to-head dimer 2 (Scheme 1) of oligosaccharide 1. which was designed to bind duplex DNA selectively at TCCTXXAGGA sequences.
机译：DNA结合分子，特别是具有序列特异性的DNA结合分子，在化学，生物学和医学领域具有巨大潜力。这样的分子可以为进一步了解DNA的化学和结构提供基础。用于分子细胞生物学工具的设计和开发，以及反义和基因疗法的开发。以加利车霉素7_1〜I为先导，我们最近合成并研究了一系列寡糖与双链DNA的结合。在这些研究中，寡糖1（方案1）作为最有效和选择性的分子出现，在TCCT位点结合双链DNA，亲和常数为K_aapprox = 10〜6M〜（-1）。 1990年在我们的实验室中首次合成。寡糖1最近由Crabtree.et等人显示。特异性抑制转录复合物。适当设计的1的寡聚物应在效价和特异性方面表现出与双链DNA的增强结合。现在，我们希望报告寡糖1的头对头二聚体2（方案1）的设计和化学合成，该寡糖1被设计为在TCCTXXAGGA序列上选择性结合双链DNA。

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