Geng Lingling, Wang Zihua, Yang Xiaoliang, Li Dan, Lian Wenxi, Xiang Zhichu, Wang Weizhi, Bu Xiangli, Lai Wenjia, Hu Zhiyuan, Fang Qiaojun
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.
Theranostics. 2015 Aug 1;5(10):1154-65. doi: 10.7150/thno.12398. eCollection 2015.
To identify peptides with high affinity and specificity against human epidermal growth factor receptor 2 (HER2), a series of peptides were designed based on the structure of HER2 and its Z(HER2:342) affibody. By using a combination protocol of molecular dynamics modeling, MM/GBSA binding free energy calculations, and binding free energy decomposition analysis, two novel peptides with 27 residues, pep27 and pep27-24M, were successfully obtained. Immunocytochemistry and flow cytometry analysis verified that both peptides can specifically bind to the extracellular domain of HER2 protein at cellular level. The Surface Plasmon Resonance imaging (SPRi) analysis showed that dissociation constants (K D) of these two peptides were around 300 nmol/L. Furthermore, fluorescence imaging of peptides against nude mice xenografted with SKBR3 cells indicated that both peptides have strong affinity and high specificity to HER2 positive tumors.
为了鉴定对人表皮生长因子受体2（HER2）具有高亲和力和特异性的肽段，基于HER2及其Z(HER2:342) 亲和体的结构设计了一系列肽段。通过分子动力学建模、MM/GBSA结合自由能计算和结合自由能分解分析相结合的方法，成功获得了两个含27个残基的新型肽段pep27和pep27-24M。免疫细胞化学和流式细胞术分析证实，这两种肽段在细胞水平上均能特异性结合HER2蛋白的胞外结构域。表面等离子体共振成像（SPRi）分析表明，这两种肽段的解离常数（KD）约为300 nmol/L。此外，针对接种SKBR3细胞的裸鼠进行的肽段荧光成像表明，这两种肽段对HER2阳性肿瘤均具有强亲和力和高特异性。
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