Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides.
Sci Rep
; 12(1): 20725, 2022 12 01.
Article
em En
| MEDLINE
| ID: mdl-36456600
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Bacteriófagos
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Glioblastoma
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
França