10.6084/m9.figshare.5788893.v1
Xue-Wei Cao
Xue-Wei
Cao
Xu-Zhong Yang
Xu-Zhong
Yang
Xuan Du
Xuan
Du
Long-Yun Fu
Long-Yun
Fu
Tao-Zhu Zhang
Tao-Zhu
Zhang
Han-Wen Shan
Han-Wen
Shan
Jian Zhao
Jian
Zhao
Fu-Jun Wang
Fu-Jun
Wang
Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating peptide
Taylor & Francis Group
2018
Tumour targeting cell-penetrating peptide (TCPP)
epidermal growth factor receptor (EGFR)
EGFR binding domain
heparin-binding domain (HBD)
2018-01-16 08:42:13
Journal contribution
https://tandf.figshare.com/articles/journal_contribution/Structure_optimisation_to_improve_the_delivery_efficiency_and_cell_selectivity_of_a_tumour-targeting_cell-penetrating_peptide/5788893
<p>Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumours. Here, we reported a novel tumour targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumour cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively. In this new TCPP, a specific alpha helix structure was inserted into a repeated amino acid (AA) sequence formed by tandem multiple selected key AA residues of vaccinia growth factor (VGF), and this sequence was then fused to a tailored heparin binding domain sequence (C6H) derived from heparin-binding epidermal growth factor-like growth factor to intensify its targeting delivery ability. EHB could carry anticancer proteins such as MAP30 (Momordica Antiviral Protein 30 kDa) into EGFR-overexpressing cancer cell and inhibit cell growth, but it had a greatly reduced interaction with normal cells. These results indicated that EHB, as a novel efficient TCPP for the selective delivery of drug molecules into cancer cells, would help to improve the efficacy and safety of anti-tumour drugs.</p>