Structure–activity relationship of HER2 receptor targeting peptide and its derivatives in targeted tumor therapy

TY - JOUR

T1 - Structure–activity relationship of HER2 receptor targeting peptide and its derivatives in targeted tumor therapy

AU - Biri-Kovács, Beáta

AU - Adorján, Afrodité

AU - Szabó, Ildikó

AU - Szeder, Bálint

AU - Bősze, Szilvia

AU - Mező, Gábor

N1 - Funding Information: Funding: This research was supported by the National Research, Development and Innovation Office under grant NKFIH K119552 and NVKP_16-1-2016-0036. This work was supported by the Hungarian National Research, Development and Innovation Office (NKFIH-1157-8/2019-DT). These studies were also supported by grant (VEKOP-2.3.3-15-2017-00020) from the European Union and the State of Hungary, co-financed by the European Regional Development Fund. Funding Information: This research was supported by the National Research, Development and Innovation Office under grant NKFIH K119552 and NVKP_16-1-2016-0036. This work was supported by the Hungarian National Research, Development and Innovation Office (NKFIH-1157-8/2019-DT). These studies were also supported by grant (VEKOP-2.3.3-15-2017-00020) from the European Union and the State of Hungary, co-financed by the European Regional Development Fund. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/1/25

Y1 - 2020/1/25

N2 - 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.

AB - 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.

KW - Breast cancer

KW - HER2

KW - HER2 diagnosis

KW - Targeted tumor therapy

KW - Targeting peptide

UR - https://www.scopus.com/pages/publications/85078687927

U2 - 10.3390/biom10020183

DO - 10.3390/biom10020183

M3 - Article

C2 - 31991749

AN - SCOPUS:85078687927

SN - 2218-273X

VL - 10

JO - Biomolecules

JF - Biomolecules

IS - 2

M1 - 183

ER -