OLIGODEOXYNUCLEOSIDE BORANOPHOSPHATES--NEW DNA ANALOG

描述：一类新的修饰核酸-- 寡脱氧核苷硼磷酸盐(BH3-ODN)是等电子的， 硫代磷及其天然产物的等离子类似物 O-磷酸酯。研究表明，HB3-ODN具有独特的 属性，并具有潜在的诊断和应用前景 治疗剂。相对于正常DNA，BH3-ODN增加 亲脂性，并显著抵抗核酸酶的降解。 初步数据表明，BH3-ODN支持RNaseH诱导的裂解 核糖核酸。BH3--ODN可以通过酶法合成得到基因长度 这些片段是父母DNA的准确、互补的拷贝。一个 合成BH3的一种新的化学方法--ODN目前正在开发中 探索过了。计划进一步应用于溶液相化学。 向固相合成转变，首次使合成成为可能 具有定义的序列的离子低聚物，最高可达毫米尔级。其他 拟议工作的目标是进一步研究独特的化学和 研究了硼磷酸盐低聚物的生物学性质，并开发了一种 一套实用的新型含硼化合物。具体目标是 到：1)开发有效的化学和酶方法，以加快 任意给定长度和序列的BH3-ODN的合成 用适当的分析方法验证BH3--ODN的完整性、碱基 组成、顺序和长度。2)调查和描述 BH3--ODN的化学、生化和生物物理性质 对生物化学和治疗应用最重要的，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、代谢及其 能够与互补的DNA和RNA形成双链和三链。 3)体外检测BH3--ODN对核糖核酸酶H的激活作用 以阻止翻译和转录。4结合BH3--ODN与 适当的官能团(多肽，磷脂荧光标记， 等)以促进其细胞渗透和靶向特定细胞 类型，并检查它们的细胞定位。5)研究可行性 使用BH3-ODN来靶向人类病毒和遗传疾病。结果 将其与其他修饰后的ODN进行比较。因此，硼磷酸盐 代表着令人兴奋的新化学，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.