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+ 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.