dc.rights.license | CC-BY-NC-ND | |
dc.contributor.advisor | Externe beoordelaar - External assesor, | |
dc.contributor.author | Hu, Yijun | |
dc.date.accessioned | 2023-04-03T00:00:42Z | |
dc.date.available | 2023-04-03T00:00:42Z | |
dc.date.issued | 2023 | |
dc.identifier.uri | https://studenttheses.uu.nl/handle/20.500.12932/43754 | |
dc.description.abstract | A library of peptides targeting HER2 was established from in silico docking analysis of a pool of over 8000 preliminary sequences based on a recently developed anti-HER2 peptide KSPNPRF. The library has been synthesized by solid-phase Fmoc protocol and evaluated for their binding affinities. The peptides have a common core sequence, PNP, flanked by various amino acids and conjugated to a Cy5.5 fluorescent dye via a PEG4-K linker. Six peptides of this library have been evaluated by a magnetic beads-based fluorescence binding assay and compared to the reference KSPNPRF and a scrambled control peptide developed by the same group. With this assay, we found a KD of 49 nM for the reference, while the affinities of the six peptides of the library ranged from ~40 nM to ~2 μM. However due to the ambiguity of the data analysis, these values need to be further validated. We also report the development of a surface plasmon resonance protocol to evaluate the peptide library. For this, we have immobilised biotinylated HER2 on a streptavidin-coated chip and assessed the effect of the protein type, sensor chip, and regeneration conditions on the quality of the measurements of the KSP*, scrambled control peptide and Herceptin. While the SPR signal is sufficient, further investigations are needed to reduce non-specific binding and improve the signal quality. | |
dc.description.sponsorship | Utrecht University | |
dc.language.iso | EN | |
dc.subject | In this study, a list of promising peptides was synthesized and evaluated for their binding affinity for HER2. | |
dc.title | Development of HER2-Targeted Theranostics for Diagnosis and Treatment of Breast Cancer | |
dc.type.content | Master Thesis | |
dc.rights.accessrights | Open Access | |
dc.subject.keywords | breast cancer, HER2, peptides, peptide synthesis, ligand-receptor binding, surface plasmon resonance, binding assay | |
dc.subject.courseuu | Molecular and Cellular Life Sciences | |
dc.thesis.id | 13982 | |