IMPROVED ANTISENSE OLIGONUCLEOIDES, & THEIR SCALE UP

描述(改编自申请人的摘要)：建议 2‘-0-烷基(甲基、乙基和炔丙基)-硫代磷酸盐-核糖核酸的合成 寡核苷酸(图2)5，6，7)及其前体，即2‘-0-烷基 (甲基、乙基和propargyl)-N-protected-5‘-DMT-3’-H-Phosphonates(图2) 9，12，13)。固相寡核苷酸合成将优化为 制备链长为18-20个核苷酸的模型低聚物 结构类，5，6，7，。这些建筑将非常有价值 治疗原型确立其作为反义的抑制效力 寡核苷酸。它们有望杂交以靶向DNA或RNA 序列在很高的程度上，对各种不同的降解具有抵抗力 胞内酶，细胞摄取率高，不可逆 交联性。 这些寡核苷酸的大规模合成(最高可达10克)是通过 固相合成。原型方法将在DNA上开发 然后是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.