COMMERCIAL PRODUCTION OF DINUCLEOTIDE PHOSPHORAMIDITES

描述(改编自申请)：制作 寡核苷酸需要单体核苷亚磷酰胺 除了不断增长的链条外，还有坚实的支撑。这方面的问题 方法包括：从n-1-MERS中提纯n-Me产物的难度； 大量使用对环境有害的有机溶剂延长了时间 基于单体的合成所需的。二核苷酸的使用 亚磷酰胺合成子可能有助于解决其中的部分或全部问题 简单地用二聚体取代最后两个步骤可能会出现问题 大大提高纯度，特别是临床或临床使用的产品 诊断用途。尽管二聚体方法的可能优势 很明显，商业上没有二聚体合成子可用于这两种 试验或生产用途。GL合成公司打算填补这一空白 需要通过第一阶段的以下具体目标： 1.开发实用和高效的合成程序 亚磷酰胺二核苷酸。 2.制备四种最需要的二核苷酸(G-T，T-G，G-G， T-T)，单位为百克。 3.测试固相合成和提纯的效率 使用二聚体单元的寡核苷酸，与 杂交店，这些产品的主要制造商。 第一阶段计划的二聚体装置的准备工作将刺激 申请者生产所有16个二聚体单位。GL综合公司希望 成为十六个二核苷酸的主要商业供应商 亚磷酰胺在第二阶段结束。最终，申请人将 对脊椎改变的二聚体追求相同的目标 (硫代磷、甲基膦)支持反义药物 制作。 建议的商业应用：不可用

DESCRIPTION (Adapted from the application): Production of oligodeoxynucleotide requires monomer nucleoside phosphoramidite addition to a growing chain on a solid support. Problems of this approach include: difficulty in purifying n-me products from n-1-mers; high use of environmentally hazardous organic solvents prolonged time required for a monomer-based synthesis. Use of dinucleotide phosphoramidite synthons can possibly help solve some or all of these problems Simply substituting a dimer to replace the last two steps may greatly improve purification, especially for products for clinical or diagnostic use. Although the possible advantages of the dimer approach are clear, no dimer synthons are available commercially for either experimental or production use. GLSynthesis Inc. intends to fill this need through the following specific aims of phase I: 1. To develop practical and efficient synthetic procedures for phosphoramidite dinucleotides. 2. To prepare the four most often needed dinucleotides (G-T, T-G, G-G, T-T) in hundred gram scales. 3. To test the efficiency of solid-phase synthesis and purification of oligodeoxynucleotides using the dimeric units, in collaboration with Hybridon Inc., the major manufacturer of these products. Preparation of the dimeric units planned in phase I will stimulate the applicant to produce all sixteen dimer units. GLSynthesis hopes to become the major commercial supplier of the sixteen dinucleotide phosphoramidites by the end of phase II. Ultimately, the applicant will pursue the same goals for dimers with altered backbone (phosphorothioates, methylphosphonates) to support antisense drug production. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE