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

Journal article

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.

Authors: Geng, L; Wang, Z; Yang, X; Li, D; Lian, W

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Ivyspring International Publisher
• Journal: Theranostics
• Volume: 5
• Issue: 10
• Pages: 1154-1165
• Publication date: 2015-08-01
• DOI: 10.7150/thno.12398
• EISSN: 1838-7640
• ISSN: 1838-7640
• Language: English
• Keywords: Biophysics; Materials science; Nanotechnology; Förster resonance energy transfer; Dissociation constant; Flow cytometry; Fluorescence; Chemistry; Peptide; Biology; Surface plasmon resonance; Molecular biology; Biochemistry; Receptor