目的 合成含有新型二肽连接子的核酸适体偶联药物，评估其血清稳定性和细胞增殖抑制活性。方法 合成连接子MC-Ala-Gln-PABC-PNP（6a），并引入PEG8得到连接子MC-PEG8-Ala-Gln-PABC-PNP（6b）。将连接子的两端分别与单甲基澳瑞他汀E、靶向c-Met的核酸适配体连接，合成核酸适体偶联药物。在胎牛血清中研究核酸适体偶联药物的体外血清稳定性，利用CCK-8检测细胞活力。结果 合成的核酸适体偶联药物1a、1b、1a'、1b'具有相对良好的血清稳定性，表现出较明显的特异性细胞增殖抑制活性。结论 可以通过改变二肽并同时加入PEG8片段来提高核酸适体偶联药物的稳定性和特异性细胞增殖抑制活性。

Objective To synthesize nucleic acid aptamer-drug conjugates containing a novel dipeptide linkers and evaluate their serum stability and cell proliferation inhibitory activity. Methods The linker MC-Ala-Gln-PABC-PNP (6a) was synthesized and PEG8 was introduced to obtain the linker MC-PEG8-Ala-Gln-PABC-PNP (6b). The two ends of the linkers were connected to monomethyl auristatin E and a c-Met-targeting aptamer, respectively, to synthesize nucleic acid aptamer coupled drugs. Serum stability in vitro of nucleic acid aptamer-drug conjugates in fetal bovine serum were studied, and cell viability was detected using CCK-8 method. Results The synthesized nucleic acid aptamer-drug conjugate 1a, 1b, 1a', and 1b' had relatively good serum stability and exhibited significant specific cell proliferation inhibition activity. Conclusion The stability and specific cell proliferation inhibition activity of nucleic acid aptamer-drug conjugates can be improved by changing dipeptide and simultaneously adding PEG8 fragments.

R914;R965