富含鸟嘌呤(G)的寡核苷酸作为治疗剂已经引起了相当大的兴趣。针对表皮生长因子受体(EGFR)转染的A549细胞选择了两个富含G的适体,和它们的富含G的结构域(S13和S50)被鉴定为解释亲本适体的结合。圆二色性(CD)光谱显示S13和S50通过形成平行的四链体与其靶标结合。他们的约束力,内化,通过流式细胞术和3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑(MTS)测定法研究了癌细胞和非癌细胞的抗增殖活性,并与核仁素结合AS1411和凝血酶结合适体进行了比较。两个截短的适体(S13和S50)在癌细胞和非癌细胞中具有良好的结合和内化作用;然而,只有S50与AS1411相似,显示出对癌细胞的有效抗增殖。我们的数据表明,富含G的寡核苷酸的肿瘤选择性抗增殖并不直接取决于富含G的适体与细胞的结合。
Guanine (G)-rich oligonucleotides have attracted considerable interest as therapeutic agents. Two G-rich
aptamers were selected against epidermal growth factor receptor (EGFR)-transfected A549 cells, and their G-rich domains (S13 and S50) were identified to account for the binding of parental
aptamers. Circular dichroism (CD) spectra showed that S13 and S50 bound to their targets by forming parallel quadruplexes. Their binding, internalization, and antiproliferation activity in cancer and noncancer cells were investigated by flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and compared with those of nucleolin-binding AS1411 and thrombin-binding aptamer. The two truncated
aptamers (S13 and S50) have good binding and internalization in cancer cells and noncancer cells; however, only S50, similar to AS1411, shows potent antiproliferation against cancer cells. Our data suggest that tumor-selective antiproliferation of G-rich oligonucleotides does not directly depend on the binding of the G-rich aptamer to cells.