目的 合成含有新型二肽連接子的核酸適體偶聯(lián)藥物，評估其血清穩(wěn)定性和細(xì)胞增殖抑制活性。方法 合成連接子MC-Ala-Gln-PABC-PNP（6a），并引入PEG8得到連接子MC-PEG8-Ala-Gln-PABC-PNP（6b）。將連接子的兩端分別與單甲基澳瑞他汀E、靶向c-Met的核酸適配體連接，合成核酸適體偶聯(lián)藥物。在胎牛血清中研究核酸適體偶聯(lián)藥物的體外血清穩(wěn)定性，利用CCK-8檢測細(xì)胞活力。結(jié)果 合成的核酸適體偶聯(lián)藥物1a、1b、1a'、1b'具有相對良好的血清穩(wěn)定性，表現(xiàn)出較明顯的特異性細(xì)胞增殖抑制活性。結(jié)論 可以通過改變二肽并同時(shí)加入PEG8片段來提高核酸適體偶聯(lián)藥物的穩(wěn)定性和特異性細(xì)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