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Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold
Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this r...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052545/ https://www.ncbi.nlm.nih.gov/pubmed/35495466 http://dx.doi.org/10.1039/d0ra00427h |
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author | Yimchuen, Wanaporn Kadonosono, Tetsuya Ota, Yumi Sato, Shinichi Kitazawa, Maika Shiozawa, Tadashi Kuchimaru, Takahiro Taki, Masumi Ito, Yuji Nakamura, Hiroyuki Kizaka-Kondoh, Shinae |
author_facet | Yimchuen, Wanaporn Kadonosono, Tetsuya Ota, Yumi Sato, Shinichi Kitazawa, Maika Shiozawa, Tadashi Kuchimaru, Takahiro Taki, Masumi Ito, Yuji Nakamura, Hiroyuki Kizaka-Kondoh, Shinae |
author_sort | Yimchuen, Wanaporn |
collection | PubMed |
description | Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this report, a method to create a HER2-binding fluctuation-regulated affinity protein (HBP-FLAP) consisting of a fibronectin type III domain (FN3) scaffold with a structurally immobilized HBP is presented. HBPs were selected by phage-library screening and grafted onto FN3 to create FN3-HBPs, and the HBP-FLAP with the highest affinity (HBP sequence: YCAHNM) was identified after affinity maturation of the grafted HBP. HBP-FLAP containing the YCAHNM peptide showed increased proteolysis-resistance, binding to HER2 with a dissociation constant (K(D)) of 58 nM in ELISA and 287 nM in biolayer interferometry and specifically detects HER2-expressing cancer cells. In addition, HBP-FLAP clearly delineated HER2-expressing tumors with a half-life of 6 h after intravenous injection into tumor-bearing mice. FN3-based FLAP is an excellent platform for developing target-binding small proteins for clinical applications. |
format | Online Article Text |
id | pubmed-9052545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90525452022-04-29 Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold Yimchuen, Wanaporn Kadonosono, Tetsuya Ota, Yumi Sato, Shinichi Kitazawa, Maika Shiozawa, Tadashi Kuchimaru, Takahiro Taki, Masumi Ito, Yuji Nakamura, Hiroyuki Kizaka-Kondoh, Shinae RSC Adv Chemistry Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this report, a method to create a HER2-binding fluctuation-regulated affinity protein (HBP-FLAP) consisting of a fibronectin type III domain (FN3) scaffold with a structurally immobilized HBP is presented. HBPs were selected by phage-library screening and grafted onto FN3 to create FN3-HBPs, and the HBP-FLAP with the highest affinity (HBP sequence: YCAHNM) was identified after affinity maturation of the grafted HBP. HBP-FLAP containing the YCAHNM peptide showed increased proteolysis-resistance, binding to HER2 with a dissociation constant (K(D)) of 58 nM in ELISA and 287 nM in biolayer interferometry and specifically detects HER2-expressing cancer cells. In addition, HBP-FLAP clearly delineated HER2-expressing tumors with a half-life of 6 h after intravenous injection into tumor-bearing mice. FN3-based FLAP is an excellent platform for developing target-binding small proteins for clinical applications. The Royal Society of Chemistry 2020-04-17 /pmc/articles/PMC9052545/ /pubmed/35495466 http://dx.doi.org/10.1039/d0ra00427h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Yimchuen, Wanaporn Kadonosono, Tetsuya Ota, Yumi Sato, Shinichi Kitazawa, Maika Shiozawa, Tadashi Kuchimaru, Takahiro Taki, Masumi Ito, Yuji Nakamura, Hiroyuki Kizaka-Kondoh, Shinae Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold |
title | Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold |
title_full | Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold |
title_fullStr | Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold |
title_full_unstemmed | Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold |
title_short | Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold |
title_sort | strategic design to create her2-targeting proteins with target-binding peptides immobilized on a fibronectin type iii domain scaffold |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052545/ https://www.ncbi.nlm.nih.gov/pubmed/35495466 http://dx.doi.org/10.1039/d0ra00427h |
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