Suppression of smooth muscle cell proliferation by a c-myc RNA-cleaving deoxyribozyme
Suppression of smooth muscle cell proliferation by a c-myc RNA-cleaving deoxyribozyme
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DOI：
10.1074/jbc.274.24.17236
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发表时间：
1999-06-11
影响因子：
4.8
通讯作者：
King, A
中科院分区：
文献类型：
--
作者：
Sun, LQ;Cairns, MJ;King, A
一种靶向c-myc RNA的小催化DNA分子被发现是平滑肌细胞（SMC）增殖的有效抑制剂。该分子的催化结构域基于先前通过体外选择衍生的催化结构域（Santoro，S，W，和Joyce，G，F，（1997）Proc. Natl，Acad. Sci. U.S.A.94，4262-4266），并且被称为“10-23”通用RNA切割脱氧核酶。除了在低浓度下抑制SMC增殖之外，发现该分子（靶向c-myc RNA的翻译起始区）在体外有效地切割其全长底物并下调平滑肌细胞中的c-myc基因表达。通过在3 '-末端包含3'-3 '-核苷酸间倒位，该分子的血清核酸酶稳定性得到增强，而基本上不损失动力学效率。SMC抑制的程度被认为是由基板结合臂的长度的影响。这在一定程度上与多个周转条件下的短底物和单周转条件下的全长底物中的催化活性相关，其中9 + 9基臂分子产生最大活性。
A small catalytic DNA molecule targeting c-myc RNA was found to be a potent inhibitor of smooth muscle cell (SMC) proliferation. The catalytic domain of this molecule was based on that previously derived by in vitro selection (Santoro, S, W,, and Joyce, G, F, (1997) Proc. Natl, Acad. Sci. U.S.A. 94, 4262-4266) and is known as the "10-23" general purpose RNA-cleaving deoxyribozyme, In addition to inhibiting SMC proliferation at low concentration, this molecule (targeting the translation initiation region of c-myc RNA) was found to efficiently cleave its full-length substrate in vitro and downregulate c-myc gene expression in smooth muscle cells. The serum nuclease stability of this molecule was enhanced without substantial loss of kinetic efficiency by inclusion of a 3'-3'-internucleotide inversion at the 3'-terminal. The extent of SMC suppression was found to be influenced by the length of the substrate binding arms. This correlated to some extent with catalytic activity in both the short substrate under multiple turnover conditions and the full-length substrate under single turnover conditions, with the 9 + 9 base arm molecule producing the greatest activity.