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为了探讨 Ａ Ｓ Ｏ Ｄ Ｎ 化学修饰形式与 Ａ Ｓ Ｏ Ｄ Ｎ 稳定性，体外细胞毒性以及抗流感病毒活性之间的关系，合成了 ７ 种不同化学修饰形式的 Ａ Ｓ Ｏ Ｄ Ｎ：硫代 Ａ Ｓ Ｏ Ｄ Ｎ 及其 ３′端分别磷酸化和胆固醇修饰；３′与 ５′端硫代，中间为天然结构的混合骨架 Ａ Ｓ Ｏ Ｄ Ｎ；天然结构 Ａ Ｓ Ｏ Ｄ Ｎ 及其 ３′端分别磷酸化和胆固醇修饰等．测定了 ７ 种修饰体在小鼠血清， Ｍ Ｄ Ｃ Ｋ 细胞裂解液，含 ２％ 胎牛血清的 Ｄ Ｍ Ｅ Ｍ培养液以及水中的稳定性，体外细胞毒性和在细胞水平抗流感病毒活性．结果表明，混合骨架 Ａ Ｓ Ｏ Ｄ Ｎ，硫代 Ａ Ｓ Ｏ Ｄ Ｎ 及其 ３′端接磷酸和胆固醇的修饰形式在小鼠血清， Ｍ Ｄ Ｃ Ｋ 细胞裂解液与含２％ 胎牛血清的 Ｄ Ｍ Ｅ Ｍ 培养液中稳定性相对较高，作用 ２４～４８ ｈ 仅混合骨架 Ａ Ｓ Ｏ Ｄ Ｎ 与硫代 Ａ Ｓ Ｏ Ｄ Ｎ 发生部分降解；天然结构 Ａ Ｓ Ｏ Ｄ Ｎ 及其 ３′端接磷酸和胆固醇修饰体在 ２４ ｈ 内大部分降解．所有 Ａ Ｓ Ｏ Ｄ Ｎ 修饰体在水中具有很高稳定性，４８ ｈ 内未见降解作用．７ 种 Ａ Ｓ Ｏ Ｄ Ｎ 修饰形式在 Ｍ Ｄ Ｃ Ｋ 细胞中未表现明显的细胞毒性．硫代 Ａ Ｓ Ｏ Ｄ Ｎ 及其 ３′端接磷酸和胆
In order to investigate the relationship between the chemical modification of A S O D N and the stability of A S O D N, cytotoxicity in vitro and anti-influenza virus activity, seven different chemically modified forms of A S O D N were synthesized: Thio A S O D N and its 3 ’end phosphorylation and cholesterol modification respectively; 3’ and 5 ’end thio, the middle structure of the mixed backbone A S O D N; natural structure A S O D N and its 3’ end Respectively phosphorylation and cholesterol modification. The stability of seven modified products in mouse serum, MCSC cell lysate, DMEM medium containing 2% fetal bovine serum and water, cytotoxicity in vitro and anti-influenza virus activity at the cellular level were measured. The results showed that the modified form of mixed backbone A S D N, thio A S O D N and its 3 ’terminal phosphate and cholesterol were tested in mouse serum, MCDT cell lysate and 2% fetal bovine serum Of D M E M medium had relatively high stability. Only 24 h to 48 h, only partial degradation of A S O D N and S-D O N was observed. The natural structure A S O D N and its 3 Terminated phosphate and cholesterol modifiers were mostly degraded within 24 h. All A S O D N modification has high stability in water, no degradation within 48 h. The seven A S O D N modified forms did not show significant cytotoxicity in MDCs cells. Thio-A S O D N and its 3 ’-terminal phosphate and gall