SYNTHESIS OF POLYRIBONUCLEOTIDES OF DEFINED SEQUENCE

具有确定序列的多核糖核苷酸的合成

• 批准号: 3269629
• 负责人: PETER T GILHAM
• 金额: $ 14.58万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269629
• 关键词: RNA; biomedical automation; chemical information system; conformation; hydrogen bond; nucleic acid chemical synthesis; nucleic acid sequence; oligonucleotides; quantum chemistry; thermodynamics

An automated solid phase system for the rapid synthesis of oligoribonucleotides will be developed. it will use the o- nitrobenzyl group for protection of ribonucleoside 2' hydroxyls and a versatile glass-based support incorporating a novel linker mechanism. New analytical methods will be designed for RNA oligomers, to ascertain their purity and confirm their homogeneity with respect to the 3'-5' linkage. The synthetic methods will first be employed to prepare a number of sets of oligonucleotides as models for the study of RNA hairpin structures, using UV and NMR spectroscopy, and X-ray crystallography. This investigation will focus on the effects of loop sequence and size on hairpin shape and stability. The solid phase system will also be adapted to provide special oligonucleotides that can be joined enzymatically to produce large RNA molecules for the study of more complex secondary structure. The oligonucleotides will carry novel terminal protecting groups to bring about the desired specific ligations. The results of these investigations are expected to contribute to methods for prediction of the secondary structures of ribonucleic acids from their sequences, and should aid studies of structure- function relationships in human RNA viruses.

一种用于快速合成的自动化固相系统 将开发寡核苷酸。它将使用o- 保护核糖核苷2‘-羟基的硝基苄基 以及结合了新型连接物的多功能玻璃基支撑体 机制。将为RNA设计新的分析方法 齐聚物，以确定其纯度并确认其 关于3‘-5’连接的同质性。合成材料 首先将使用方法来准备一组 寡核苷酸作为研究RNA发夹的模型 结构，用UV和核磁共振光谱和X-射线 结晶学。这项调查将重点放在 环的顺序和大小对发夹形状和稳定性的影响。坚固的 相位系统也将改装为提供特殊的 可以通过酶连接产生的寡核苷酸 大分子RNA用于研究更复杂的二次 结构。寡核苷酸将携带新的末端 保护基团以实现所需的特定连接。 这些调查的结果预计将有助于 预测核糖核二级结构的方法 从它们的序列中分离出酸，并应该有助于结构的研究- 人类RNA病毒中的功能关系。