结合
喜树碱
曲妥珠单抗
化学
肽
单克隆抗体
寡肽
抗体-药物偶联物
抗体
药理学
生物信息学
癌症研究
生物化学
癌症
生物
免疫学
医学
内科学
乳腺癌
数学分析
基因
数学
作者
Jiaqi Zhou,Yuxing Zou,Yanjun Cai,Fanglian Chi,Wenlong Huang,Wei Shi,Hai Qian
标识
DOI:10.1016/j.bioorg.2021.105453
摘要
Human epidermal growth factor receptor 2 (HER2) has been recognized as an important therapeutic target for its overexpression in many cancers. Trastuzumab is a monoclonal antibody targeting HER2, which has been approved by FDA to treat HER2-positive cancer. In this research, cyclic peptide Cyclo-GCGPep1 was designed based on the binding mode between antibody and HER2 protein in silico, which has been confirmed possessing good affinity with HER2. Cyclo-GCGPep1 was also used to construct peptide-drug conjugates with Camptothecin. Biological evaluations demonstrated that Conjugate 1 has a good antiproliferative activity on SK-BR-3 and NCI-N87 cells. Conjugate 1 retained the pro-apoptotic and Topo I inhibitory ability of Camptothecin. Meanwhile, it has good targeting ability towards HER2-positive cells with the help of Cyclo-GCGPep1. It also has better permeability in the tumor spheroid model than Camptothecin. In summary, the design of cyclic peptide derived from antibody is of significance for the discovery of targeting peptides and Conjugate 1 is expected as a good therapeutic agent for HER2-positive cancers.
科研通智能强力驱动
Strongly Powered by AbleSci AI