Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors.
Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors.
复制标题
基于结构的设计对 HER2 阳性肿瘤具有高亲和力和特异性的肽
作者：
Geng L;Wang Z;Yang X;Li D;Lian W;Xiang Z;Wang W;Bu X;Lai W;Hu Z;Fang Q
根据人表皮生长因子受体2(HER2)及其Z(HER2：342)亲和体的结构设计了一系列抗人表皮生长因子受体2(HER2)高亲和力和高特异性的多肽。通过分子动力学模拟、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，成功地获得了两个含27个残基的新多肽：多肽27和多肽27-24M。免疫细胞化学和流式细胞仪分析证实，两种多肽均能在细胞水平上与HER2蛋白的胞外区特异性结合。表面等离子体共振成像(SPRI)分析表明，这两种多肽的解离常数(Kd)均在300nmol/L左右。此外，对裸鼠移植SKBR3细胞的荧光成像表明，这两种多肽对HER2阳性肿瘤均具有较强的亲和力和较高的特异性。
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 (KD) 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.