聚乙二醇修饰的多肽-阿霉素偶联物的合成及其性能  

Synthesis and properties of a PEG modified peptide-doxorubicin conjugate

作　　者：刘祺 李松涛[1] 赵桂琴[1] LIUU Qi;LI Song-tao;ZHAO Gui-qin(Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine,Institute of Chinese Materia Medica,Chengde Medical University,Chengde,Hebei 067000,China)

机构地区：[1]承德医学院中药研究所河北省中药研究与开发重点实验室,河北承德067000

出　　处：《军事医学》2021年第3期199-203,共5页Military Medical Sciences

基　　金：承德医学院自然科学研究计划项目(201915);河北省自然科学基金(H2017406022);河北省高等学校科学技术研究青年拔尖人才计划项目(BJ2017055);河北省高校重点学科建设项目(冀教高[2013]4)。

摘　　要：目的合成聚乙二醇(PEG)修饰的多肽-阿霉素(DOX)偶联物,并评价其性能。方法以异官能团双取代的PEG衍生物为交联剂,将转铁蛋白受体(TfR)特异性结合多肽类似物与DOX偶联,合成一种PEG修饰的多肽-阿霉素偶联物,MALDI-TOF MS予以表征。通过考察该偶联物的体外血清稳定性、体外HepG2肝癌细胞增殖抑制活性及其在不同浓度还原性谷胱甘肽(GSH)溶液中的降解特性等评价其性能。结果 PEG修饰的多肽-阿霉素偶联物的体外血清半衰期为(1.92±0.13)h,其在5 mmol/L GSH溶液中的降解效率高于5μmol/L GSH溶液。该偶联物对HepG2细胞的IC50值为(68.47±4.99)μmol/L。结论合成的PEG修饰的多肽-阿霉素偶联物具有还原响应性降解特性,其对HepG2细胞具有一定的体外增殖抑制活性。Objective To synthesize a polyethylene glycol(PEG)modified peptide-doxorubicin(DOX)conjugate,and evaluate its properties. Methods A PEG-modified peptide-DOX conjugate was synthesized by connecting a transferrin receptor(TfR)targeted binding peptide analog with DOX via a hetero-functional disubstituted PEG derivative as the crosslinker and was characterized by MALDI-TOF MS. The in vitro serum stability,antiproliferative activity against HepG2 liver cancer cells and degradation character of this conjugate at different concentrations of glutathione(GSH)solution were investigated to evaluate its properties. Results The in vitro serum half life of the PEG modified peptide-DOX conjugate was(1.92±0.13)h,and its degradation efficiency in 5 mmol/L GSH solution was higher than that in 5 μmol/L GSH solution. The IC50 value of this conjugate against HepG2 cells was(68.47±4.99)μmol/L. Conclusion The synthetic PEG modified peptide-DOX conjugate is capable of reduction responsive degradation,and shows some in vitro antiproliferative activity against HepG2 cells.

关 键 词：转铁蛋白受体 聚乙二醇 阿霉素 抗肿瘤药 谷胱甘肽 

分 类 号：R979.1[医药卫生—药品]