Loop长度对G -四链体DNA识别和结合肿瘤细胞的能力的影响

Effect of G-quadruplex’s Loop Length on Its Recognition and Combination with Tumor Cells

G-四链体是由富含鸟嘌呤(G)的核酸通过π-π堆积形成的核酸二级结构。前期研究发现,G-四链体DNA对肿瘤细胞具有普遍识别和结合能力,且具有如抗肿瘤增殖等生物学活性,但G-四链体DNA的结构对其识别和结合肿瘤细胞的能力的影响还未见报道。本文采用圆二色光谱和凝胶电泳对不同连接环(loop)长度G-四链体DNA的结构和稳定性进行了研究,利用流式细胞术和激光共聚焦显微成像技术,研究了G-四链体DNA的连接环(loop)长度在其与肿瘤细胞结合中的作用。结果表明,loop长度越短的G-四链体DNA越易形成平行结构,识别和结合肿瘤细胞的能力越强,也更容易被细胞摄取;loop长度长的G-四链体DNA倾向于形成混合平行结构,这类G-四链体DNA识别和结合肿瘤细胞的能力较弱。

G-quadruplex is a nucleic acid secondary structure formed byπ-πstacking of guanine-rich nucleic acid sequence through the G plane.Previous studies have found that G-quadruplex DNA has universal ability to recognize tumor cells and possesses a variety of biological activities,such as anti-tumor activity.However,the effect of G-quadruplex DNA structure on its ability of cell recognition is far from being understood.In this paper,circular dichroism spectra and gel electrophoresis were used to investigate structural stability of G-quadruplex with different loop lengths.We also investigated their binding ability with different cancer cells by flow cytometry and confocal imaging.The results showed that the shorter loop was likely to form a parallel structure,which led to stronger anti-nuclease stability and better ability in recognizing and binding to cells.And short loop permitted cellular internalization of G-quadruplex easier as well.