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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...

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Autores principales: Yimchuen, Wanaporn, Kadonosono, Tetsuya, Ota, Yumi, Sato, Shinichi, Kitazawa, Maika, Shiozawa, Tadashi, Kuchimaru, Takahiro, Taki, Masumi, Ito, Yuji, Nakamura, Hiroyuki, Kizaka-Kondoh, Shinae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
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.
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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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