A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.

Peptides that have high affinity for target molecules on the surface of cancer cells are crucial for the development of targeted cancer therapies. However, unstructured peptides often fail to bind their target molecules with high affinity. To efficiently identify high-affinity target-binding peptide...

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Autores principales:	Tetsuya Kadonosono, Etsuri Yabe, Tadaomi Furuta, Akihiro Yamano, Takuya Tsubaki, Takuya Sekine, Takahiro Kuchimaru, Minoru Sakurai, Shinae Kizaka-Kondoh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29142f9390054aa7838d3365c9687601
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id	oai:doaj.org-article:29142f9390054aa7838d3365c9687601
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spelling	oai:doaj.org-article:29142f9390054aa7838d3365c96876012021-11-25T06:06:18ZA fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.1932-620310.1371/journal.pone.0103397https://doaj.org/article/29142f9390054aa7838d3365c96876012014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25084350/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Peptides that have high affinity for target molecules on the surface of cancer cells are crucial for the development of targeted cancer therapies. However, unstructured peptides often fail to bind their target molecules with high affinity. To efficiently identify high-affinity target-binding peptides, we have constructed a fluorescent protein scaffold, designated gFPS, in which structurally constrained peptides are integrated at residues K131-L137 of superfolder green fluorescent protein. Molecular dynamics simulation supported the suitability of this site for presentation of exogenous peptides with a constrained structure. gFPS can present 4 to 12 exogenous amino acids without a loss of fluorescence. When gFPSs presenting human epidermal growth factor receptor type 2 (HER2)-targeting peptides were added to the culture medium of HER2-expressing cells, we could easily identify the peptides with high HER2-affinity and -specificity based on gFPS fluorescence. In addition, gFPS could be expressed on the yeast cell surface and applied for a high-throughput screening. These results demonstrate that gFPS has the potential to serve as a powerful tool to improve screening of structurally constrained peptides that have a high target affinity, and suggest that it could expedite the one-step identification of clinically applicable cancer cell-binding peptides.Tetsuya KadonosonoEtsuri YabeTadaomi FurutaAkihiro YamanoTakuya TsubakiTakuya SekineTakahiro KuchimaruMinoru SakuraiShinae Kizaka-KondohPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103397 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tetsuya Kadonosono Etsuri Yabe Tadaomi Furuta Akihiro Yamano Takuya Tsubaki Takuya Sekine Takahiro Kuchimaru Minoru Sakurai Shinae Kizaka-Kondoh A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
description	Peptides that have high affinity for target molecules on the surface of cancer cells are crucial for the development of targeted cancer therapies. However, unstructured peptides often fail to bind their target molecules with high affinity. To efficiently identify high-affinity target-binding peptides, we have constructed a fluorescent protein scaffold, designated gFPS, in which structurally constrained peptides are integrated at residues K131-L137 of superfolder green fluorescent protein. Molecular dynamics simulation supported the suitability of this site for presentation of exogenous peptides with a constrained structure. gFPS can present 4 to 12 exogenous amino acids without a loss of fluorescence. When gFPSs presenting human epidermal growth factor receptor type 2 (HER2)-targeting peptides were added to the culture medium of HER2-expressing cells, we could easily identify the peptides with high HER2-affinity and -specificity based on gFPS fluorescence. In addition, gFPS could be expressed on the yeast cell surface and applied for a high-throughput screening. These results demonstrate that gFPS has the potential to serve as a powerful tool to improve screening of structurally constrained peptides that have a high target affinity, and suggest that it could expedite the one-step identification of clinically applicable cancer cell-binding peptides.
format	article
author	Tetsuya Kadonosono Etsuri Yabe Tadaomi Furuta Akihiro Yamano Takuya Tsubaki Takuya Sekine Takahiro Kuchimaru Minoru Sakurai Shinae Kizaka-Kondoh
author_facet	Tetsuya Kadonosono Etsuri Yabe Tadaomi Furuta Akihiro Yamano Takuya Tsubaki Takuya Sekine Takahiro Kuchimaru Minoru Sakurai Shinae Kizaka-Kondoh
author_sort	Tetsuya Kadonosono
title	A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
title_short	A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
title_full	A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
title_fullStr	A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
title_full_unstemmed	A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
title_sort	fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/29142f9390054aa7838d3365c9687601
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A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides.

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