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

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硅基保护基团。RNA的合成比DNA更难，因为需要更复杂的核苷单体保护方案。5-硅基-2-正构酯（2-ACE）策略解决了这一问题，并提供了高纯度和高产量的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。这样的研究绝对需要合成寡核苷酸，这些寡核苷酸通常包含修饰，而且没有其他方法可以合成。这项SBIR I期提案的目标是降低成本并提高RNA合成的可靠性，以便向科学界提供酰胺。新开发的硅基将通过提高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纯化策略。用潜在的硅基候选物保护的核苷5将被检查其稳定性，在固相合成过程中是否容易脱保护，以及是否适合结合发色团进行偶联效率的实时分析。该项目的商业应用将在快速增长的RNA合成市场中支持分子生物学和药物设计的研究工作。

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.