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

Lingling Geng; Zihua Wang; Xiaoliang Yang; Dan Li; Wenxi Lian; Zhichu Xiang; Weizhi Wang; Xiangli Bu; Wenjia Lai; Zhiyuan Hu; Qiaojun Fang

doi:10.7150/thno.12398

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

Lingling Geng, Zihua Wang, Xiaoliang Yang, Dan Li, Wenxi Lian, Zhichu Xiang, Weizhi Wang, Xiangli Bu, Wenjia Lai, Zhiyuan Hu^*, Qiaojun Fang

^*Corresponding author for this work

National Center for Nanoscience and Technology

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1154-1165
Number of pages	12
Journal	Theranostics
Volume	5
Issue number	10
DOIs	https://doi.org/10.7150/thno.12398
Publication status	Published - 2015
Externally published	Yes

Keywords

HER2 targeted peptide
MD simulation
breast cancer
structure-based design

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7150/thno.12398

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title = "Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors",

abstract = "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.",

keywords = "HER2 targeted peptide, MD simulation, breast cancer, structure-based design",

author = "Lingling Geng and Zihua Wang and Xiaoliang Yang and Dan Li and Wenxi Lian and Zhichu Xiang and Weizhi Wang and Xiangli Bu and Wenjia Lai and Zhiyuan Hu and Qiaojun Fang",

note = "Publisher Copyright: {\textcopyright} 2015 Ivyspring International Publisher.",

year = "2015",

doi = "10.7150/thno.12398",

language = "English",

volume = "5",

pages = "1154--1165",

journal = "Theranostics",

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T1 - Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors

AU - Geng, Lingling

AU - Wang, Zihua

AU - Yang, Xiaoliang

AU - Li, Dan

AU - Lian, Wenxi

AU - Xiang, Zhichu

AU - Wang, Weizhi

AU - Bu, Xiangli

AU - Lai, Wenjia

AU - Hu, Zhiyuan

AU - Fang, Qiaojun

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - HER2 targeted peptide

KW - MD simulation

KW - breast cancer

KW - structure-based design

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U2 - 10.7150/thno.12398

DO - 10.7150/thno.12398

M3 - Article

C2 - 26284145

AN - SCOPUS:84945898755

SN - 1838-7640

VL - 5

SP - 1154

EP - 1165

JO - Theranostics

JF - Theranostics

IS - 10

ER -

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

Abstract

Keywords

UN SDGs

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