Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors

被引：34

作者：

Geng, Lingling ^{[1
]}

Wang, Zihua ^{[1
]}

Yang, Xiaoliang ^{[1
]}

Li, Dan ^{[1
]}

Lian, Wenxi ^{[1
]}

Xiang, Zhichu ^{[1
]}

Wang, Weizhi ^{[1
]}

Bu, Xiangli ^{[1
]}

Lai, Wenjia ^{[1
]}

Hu, Zhiyuan ^{[1
]}

Fang, Qiaojun ^{[1
]}

机构：

[1] Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China

来源：

THERANOSTICS | 2015年 / 5卷 / 10期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

structure-based design; HER2 targeted peptide; breast cancer; MD simulation; STAPHYLOCOCCAL PROTEIN-A; FREE-ENERGY CALCULATIONS; BREAST-CANCER; MOLECULAR-MECHANICS; AFFIBODY MOLECULES; CONTINUUM MODELS; BINDING; INSIGHTS; ONCOGENE; LIGANDS;

D O I：

10.7150/thno.12398

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：1154 / 1165

页数：12

共 57 条

[1] Molecular Imaging of HER2-Expressing Malignant Tumors in Breast Cancer Patients Using Synthetic 111In- or 68Ga-Labeled Affibody Molecules [J].