IMPROVED ANTISENSE OLIGONUCLEOIDES, & THEIR SCALE UP

描述（改编自申请人摘要）：拟 合成2 ′-O-烷基（甲基、乙基和炔丙基）-硫代膦酸酯-ribo 寡核苷酸（图5、6、7）及其前体，即2 '-O-烷基 （甲基、乙基和炔丙基）-N-保护的-5 '-DMT-3'-H-膦酸酯（图 9、12、13）。 将优化固相寡核苷酸合成， 产生链长18-20个核苷酸长的模型寡聚体， 类结构，5，6，7，. 这些建筑物将非常有价值 治疗原型，以建立其作为反义的抑制效力 寡核苷酸 预期它们与靶DNA或RNA杂交 序列在高度，具有抵抗降解的各种 细胞内酶，高细胞摄取，易受不可逆 交联。 这些寡核苷酸的大规模合成（高达10 gm）建议通过 固相合成 原型方法将在DNA上开发， 系列，接着是2 '-烷基系列中的一个寡核苷酸。

DESCRIPTION (Adapted from applicant's abstract):It is proposed to synthesize 2'-0-alkyl (methyl, ethyl and propargyl)-thiophosphonate-ribo Oligonucleotides (fig. 5,6,7) and their precursors, viz; 2'-0-alkyl (methyl, ethyl, and propargyl)-N-protected-5'-DMT-3'-H-Phosphonates (fig. 9,12,13). Solid phase Oligonucleotide synthesis would be optimized to produce model oligomers of the chain-length 18-20 nucleotide long in the class of structures, 5,6,7,. These structures would be extremely valuable therapeutics prototypes to establish their inhibitory potency as antisense oligonucleotides. They are expected to hybridize to target DNA or RNA sequences at high degree, have resistance to degradation by various intracellular enzymes, high cellular up take, amenable to irreversible cross-linking. Large scale synthesis of these oligonucleotides (upto 10gm) is proposed via solid phase synthesis. The prototype method would be developed on the DNA series, followed by one oligonucleotide in 2'-alkyl series.