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Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides
We report here the selection and characterization of a novel peptide ligand using phage display targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in several kinds of cancer: ovarian cancer, breast cancer...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715707/ https://www.ncbi.nlm.nih.gov/pubmed/36456600 http://dx.doi.org/10.1038/s41598-022-25257-4 |
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author | Mansour, Sourour Adhya, Indranil Lebleu, Coralie Dumpati, Rama Rehan, Ahmed Chall, Santu Dai, Jingqi Errasti, Gauthier Delacroix, Thomas Chakrabarti, Raj |
author_facet | Mansour, Sourour Adhya, Indranil Lebleu, Coralie Dumpati, Rama Rehan, Ahmed Chall, Santu Dai, Jingqi Errasti, Gauthier Delacroix, Thomas Chakrabarti, Raj |
author_sort | Mansour, Sourour |
collection | PubMed |
description | We report here the selection and characterization of a novel peptide ligand using phage display targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in several kinds of cancer: ovarian cancer, breast cancer and glioblastoma, but not in normal tissues. A 12-mer random peptide library was screened against EGFRvIII. Phage-selected peptides were sequenced in high-throughput by next generation sequencing (NGS), and their diversity was studied to identify highly abundant clones expected to bind with the highest affinities to EGFRvIII. The enriched peptides were characterized and their binding capacity towards stable cell lines expressing EGFRvIII, EGFR wild type (EGFR WT), or a low endogenous level of EGFR WT was confirmed by flow cytometry analysis. The best peptide candidate, VLGREEWSTSYW, was synthesized, and its binding specificity towards EGFRvIII was validated in vitro. Additionally, computational docking analysis suggested that the identified peptide binds selectively to EGFRvIII. The novel VLGREEWSTSYW peptide is thus a promising EGFRvIII-targeting agent for future applications in cancer diagnosis and therapy. |
format | Online Article Text |
id | pubmed-9715707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97157072022-12-03 Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides Mansour, Sourour Adhya, Indranil Lebleu, Coralie Dumpati, Rama Rehan, Ahmed Chall, Santu Dai, Jingqi Errasti, Gauthier Delacroix, Thomas Chakrabarti, Raj Sci Rep Article We report here the selection and characterization of a novel peptide ligand using phage display targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in several kinds of cancer: ovarian cancer, breast cancer and glioblastoma, but not in normal tissues. A 12-mer random peptide library was screened against EGFRvIII. Phage-selected peptides were sequenced in high-throughput by next generation sequencing (NGS), and their diversity was studied to identify highly abundant clones expected to bind with the highest affinities to EGFRvIII. The enriched peptides were characterized and their binding capacity towards stable cell lines expressing EGFRvIII, EGFR wild type (EGFR WT), or a low endogenous level of EGFR WT was confirmed by flow cytometry analysis. The best peptide candidate, VLGREEWSTSYW, was synthesized, and its binding specificity towards EGFRvIII was validated in vitro. Additionally, computational docking analysis suggested that the identified peptide binds selectively to EGFRvIII. The novel VLGREEWSTSYW peptide is thus a promising EGFRvIII-targeting agent for future applications in cancer diagnosis and therapy. Nature Publishing Group UK 2022-12-01 /pmc/articles/PMC9715707/ /pubmed/36456600 http://dx.doi.org/10.1038/s41598-022-25257-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mansour, Sourour Adhya, Indranil Lebleu, Coralie Dumpati, Rama Rehan, Ahmed Chall, Santu Dai, Jingqi Errasti, Gauthier Delacroix, Thomas Chakrabarti, Raj Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides |
title | Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides |
title_full | Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides |
title_fullStr | Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides |
title_full_unstemmed | Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides |
title_short | Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides |
title_sort | identification of a novel peptide ligand for the cancer-specific receptor mutation egfrviii using high-throughput sequencing of phage-selected peptides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715707/ https://www.ncbi.nlm.nih.gov/pubmed/36456600 http://dx.doi.org/10.1038/s41598-022-25257-4 |
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