Synthetic Methodologies for Molecular Imaging: Synthesis, Cyclization and In Vitro Binding Study of Death Receptor 5 Targeted Peptides
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Date
2018-06-13
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Johns Hopkins University
Abstract
Molecular Imaging (MI) techniques are rapidly developed to achieve precise, early and in-time diagnosis for various disease. Unlike conventional anatomical imaging technique, non-invasive molecular imaging has paved a novel way for disease study and diagnosis on a molecular level in living organism without intervention on its biological process. Molecular imaging can allow clinicians to gain more information on precise localization, visualization of the disease. One strategy to visualize certain disease is to target biomarker on certain cells by designed substrate specific imaging probe.
Tumor necrosis factor (TNF) - related apoptosis-inducing ligand, known as TRAIL, is a promising anticancer ligand that can biologically bind to Death Receptor 5 (DR5). Studies have showed that colorectal cancers have significant DR5 upregulation. Except in oncology, liver fibrosis is also relevant to TRAIL, which is a common chronic liver disease that will lead to liver cirrhosis and hepatocellular carcinoma. Activated hepatic stellate cells (aHSCs) is major abnormal cell types, while studies show aHSCs are associated with elevated expression of death receptors and sensitivity towards TRAIL induced cell death. In this study, five phage-display determined Death Receptor 5 (DR5) targeted peptide has been developed to visualize DR5 and apoptosis simultaneously.
In the initial stage of developing Death Receptor 5 based PET or SPECT imaging agent for living cirrhosis, fluorescent dye, 5-carboxyfluorescent, has been conjugated on the peptide for screening and binding affinity test for developing this PET/SPECT imaging agent.
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Keywords
Molecular Imaging, Peptide Synthesis