SBIR Phase I: Novel Silyl Ether Protecting Groups for RNA/DNA Synthesis

SBIR 第一阶段：用于 RNA/DNA 合成的新型硅醚保护基团

• 批准号: 0109798
• 负责人: Stephen Scaringe
• 金额: $ 10万
• 依托单位: DHARMACON INC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0109798&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; Silyl; Ether

This Small Business Research Phase I project will develop novel silyl protecting groups for RNA/DNA oligonucleotide synthesis. The synthesis of RNA is more difficult than DNA because a more complex protection scheme for nucleoside monomers is required. The 5-silyl-2-orthoester (2-ACE) strategy addresses this problem and provides RNA of excellent purity and yield. This achievement is invaluable to RNA scientists studying molecular biology or developing therapeutic strategies. Such research absolutely requires synthetic oligonucleotides that often incorporate modifications and are made by no other means. The goal of this SBIR Phase I proposal is to reduce the cost and increase the reliability of RNA synthesis so that amidites can be provided to the scientific community. The new silyl groups to be developed will facilitate nucleoside monomer preparation by improving selectivity for 5-protection and will promote economical purification strategies including crystallization. Nucleosides 5-protected with potential silyl candidates will be examined for their stability, ease of deprotection during solid phase synthesis, and amenability to incorporation of chromophores for real-time assays of coupling efficiencyThe commercial application of this project will be in the rapidly growing RNA synthesis market to support research endeavors in molecular biology and drug design.

这个小企业研究第一阶段项目将开发用于RNA/DNA寡核苷酸合成的新型甲硅烷基保护基团。RNA的合成比DNA更困难，因为需要更复杂的核苷单体保护方案。5-甲硅烷基-2-原酸酯（2-ACE）策略解决了这个问题，并提供了优异纯度和产率的RNA。这一成就对于研究分子生物学或开发治疗策略的RNA科学家来说是无价的。这种研究绝对需要合成的寡核苷酸，这些寡核苷酸通常包含修饰，并且没有其他方法。SBIR第一阶段提案的目标是降低RNA合成的成本并提高其可靠性，以便为科学界提供酰胺。待开发的新甲硅烷基将通过提高5-保护的选择性来促进核苷单体的制备，并将促进包括结晶在内的经济的纯化策略。115研究了5位硅基保护的核苷在固相合成中的稳定性、脱保护的难易性以及与发色团结合的实时偶联效率。该项目的商业应用将在快速增长的RNA合成市场中进行，以支持分子生物学和药物设计的研究工作。