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Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy

Human epidermal growth factor (HER2) is a transmembrane tyrosine kinase receptor that is frequently overexpressed in breast cancer. Its increased level prognoses a poor patient outcome and a high mortality rate. Despite the widening spectrum of therapies that are becoming available to treat HER2+ br...

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Autores principales: Biri-Kovács, Beáta, Adorján, Afrodité, Szabó, Ildikó, Szeder, Bálint, Bősze, Szilvia, Mező, Gábor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072344/
https://www.ncbi.nlm.nih.gov/pubmed/31991749
http://dx.doi.org/10.3390/biom10020183
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author Biri-Kovács, Beáta
Adorján, Afrodité
Szabó, Ildikó
Szeder, Bálint
Bősze, Szilvia
Mező, Gábor
author_facet Biri-Kovács, Beáta
Adorján, Afrodité
Szabó, Ildikó
Szeder, Bálint
Bősze, Szilvia
Mező, Gábor
author_sort Biri-Kovács, Beáta
collection PubMed
description Human epidermal growth factor (HER2) is a transmembrane tyrosine kinase receptor that is frequently overexpressed in breast cancer. Its increased level prognoses a poor patient outcome and a high mortality rate. Despite the widening spectrum of therapies that are becoming available to treat HER2+ breast cancer, its side effects and resistance still make this protein a valuable object of research in targeted tumor therapy. The role of tumor-targeting peptides has become more and more prominent in the last few decades due to their simple synthesis and pharmakokinetic properties. Here, we examine two fluorescently-labeled HER2-specific peptides and their combined analogues that are developed to target the extracellular region of HER2. The peptides are investigated on breast cancer cell lines with different HER2 expression profiles. Moreover, their extracellular localization and specificity are confirmed by flow cytometry and confocal microscopy. Therefore, a new, combined HER2 binding conjugate is obtained that interacts with HER2-overexpressing cells with high affinity and specificity. Furthermore, secondary structure prediction reveals that the α-helical content of the peptides is associated with their receptor recognition. This highly specific conjugate can be used as a starting point for diagnostical or drug-targeting purposes in upcoming studies.
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spelling pubmed-70723442020-03-19 Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy Biri-Kovács, Beáta Adorján, Afrodité Szabó, Ildikó Szeder, Bálint Bősze, Szilvia Mező, Gábor Biomolecules Article Human epidermal growth factor (HER2) is a transmembrane tyrosine kinase receptor that is frequently overexpressed in breast cancer. Its increased level prognoses a poor patient outcome and a high mortality rate. Despite the widening spectrum of therapies that are becoming available to treat HER2+ breast cancer, its side effects and resistance still make this protein a valuable object of research in targeted tumor therapy. The role of tumor-targeting peptides has become more and more prominent in the last few decades due to their simple synthesis and pharmakokinetic properties. Here, we examine two fluorescently-labeled HER2-specific peptides and their combined analogues that are developed to target the extracellular region of HER2. The peptides are investigated on breast cancer cell lines with different HER2 expression profiles. Moreover, their extracellular localization and specificity are confirmed by flow cytometry and confocal microscopy. Therefore, a new, combined HER2 binding conjugate is obtained that interacts with HER2-overexpressing cells with high affinity and specificity. Furthermore, secondary structure prediction reveals that the α-helical content of the peptides is associated with their receptor recognition. This highly specific conjugate can be used as a starting point for diagnostical or drug-targeting purposes in upcoming studies. MDPI 2020-01-25 /pmc/articles/PMC7072344/ /pubmed/31991749 http://dx.doi.org/10.3390/biom10020183 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Biri-Kovács, Beáta
Adorján, Afrodité
Szabó, Ildikó
Szeder, Bálint
Bősze, Szilvia
Mező, Gábor
Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy
title Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy
title_full Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy
title_fullStr Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy
title_full_unstemmed Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy
title_short Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy
title_sort structure–activity relationship of her2 receptor targeting peptide and its derivatives in targeted tumor therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072344/
https://www.ncbi.nlm.nih.gov/pubmed/31991749
http://dx.doi.org/10.3390/biom10020183
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