OLIGODEOXYNUCLEOSIDE BORANOPHOSPHATES--NEW DNA ANALOG

描述：一类新的修饰核酸， 寡脱氧核苷硼磷酸酯 (BH3-ODN) 是等电子的， 硫代磷酸酯和天然存在的等离子类似物 O-磷酸酯。 研究表明HB3-ODN具有独特的 特性并具有作为诊断和应用的潜力 治疗剂。 相对于正常DNA，BH3--ODN有所增加 亲脂性，并且特别能抵抗核酸酶的降解。 初步数据表明 BH3--ODN 支持 RNAse H 诱导的 核糖核酸。 BH3--ODN 可以通过酶促合成来给出基因长度 片段是母体 DNA 的准确互补副本。 一个 目前正在开发合成BH3--ODN的有前途的新化学方法 探索过。 计划进一步应用溶液相化学 固相合成，首次使合成成为可能 具有确定序列的 lon 寡核苷酸，最高可达毫摩尔级。 其他 拟议工作的目标是进一步研究独特的化学和 硼磷酸盐低聚物的生物学特性，并开发了一种 一套实用的新型硼化合物。 具体目标是 1）开发有效的化学和酶方法来加速 结合任何给定长度和序列的 BH3--ODN 的合成 采用适当的分析方法来验证 BH3--ODN 的完整性、碱基 组成、顺序和长度。 2）调查并划定 BH3--ODN 的化学、生物化学和生物物理特性是 对于生物化学和治疗应用最重要，包括 它们在生理条件下的稳定性、核酸酶抗性、 亲脂性和穿过细胞膜的能力、新陈代谢及其 与互补的 DNA 和 RNA 形成双链体和三链体的能力。 3)考察BH3--ODN体外激活RNAse H的潜力 用于阻止翻译和转录。 4 将 BH3--ODN 与 适当的官能团（肽、磷脂荧光标记、 等）以促进其细胞渗透并靶向特定细胞 类型，并检查它们的细胞定位。 5）研究可行性 利用 BH3--ODN 来靶向人类病毒和遗传疾病。 结果 将与其他修饰的ODN进行比较。 因此，硼磷酸盐 代表并令人兴奋的新化学，在此基础上建立新的诊断和 治疗技术。

DESCRIPTION: A new class of modified nucleic acids, the oligodeoxynucleoside boranophosphates (BH3-ODN), are isoelectronic and iso-ionic analogs of the phosphorothioates and the naturally occurring O-phosphate esters. Studies demonstrate that HB3-ODN possess unique properties and have potential for application as diagnostic and therapeutic agents. Relative to normal DNA, BH3--ODN have increased lipophilicity and are notably resistant to degradation by nucleases. Preliminary data suggest that BH3--ODN support RNAse H induced cleavage of RNA. BH3--ODN can by synthesized enzymatically to give gene-length fragments that are accurate, complementary copies of the parent DNA. A promising new chemical method for synthesizing BH3--ODN is currently being explored. Further applications are planned for solution phase chemistries to solid phase synthesis, making possible for the first time the synthesis of lon oligos with defined sequence, at up to millimolar scale. Other goals of the proposed work are to examine further the unique chemical and biological properties of the boranophosphate oligomers, and develop a novel set of boronated compounds for practical use. The specific aims are to: 1)Develop effective chemical and enzymatic approaches to expedite synthesis of the BH3--ODN of any given length and sequence, in conjunction with appropriate analytical methods to verify the BH3--ODN integrity, base composition, sequence, and length. 2)Investigate and delineate the chemical, biochemical, and biophysical properties of BH3--ODN which are most essential for biochemica and therapeutical applications, including their stability under physiological conditions, nuclease resistance, lipophilicity and ability to cross cell membranes, metabolism, and their ability to form duplexes and triplexes with the complementary DNA and RNA. 3)Examine the potential of BH3--ODN for activating RNAse H in vitro and for arresting translation and transcription. 4 Conjugate BH3--ODN with appropriate functional groups (peptides, phospholipids fluoresce labels, etc.) to facilitate their cell penetration and targeting to specific cell types, and to examine their cell localization. 5) Study the feasibility of employing BH3--ODN to target human viral and genetic diseases. Results will be compared with other modified ODN. Thus, boranophosphates represent and exciting new chemistry on which to build new diagnostic and therapeutic technologies.