Design and synthesis of dye-conjugated hepsin inhibitors
| Autor: | Youngjoo Byun, Hongmok Kwon, Il Minn, Taehyeong Lim, Sang Hyun Son, K.A. Kim, Doyoung Choi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Boron Compounds
Serine Proteinase Inhibitors Hepsin Conjugated system Ligands 01 natural sciences Biochemistry chemistry.chemical_compound Prostate cancer Inhibitory Concentration 50 Prostate Catalytic Domain Cell Line Tumor Drug Discovery medicine Humans Matriptase Molecular Biology Fluorescent Dyes Serine protease Binding Sites biology 010405 organic chemistry Chemistry Organic Chemistry Serine Endopeptidases medicine.disease Ligand (biochemistry) 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry medicine.anatomical_structure Drug Design biology.protein BODIPY |
| Zdroj: | Bioorganic chemistry. 89 |
| ISSN: | 1090-2120 |
| Popis: | Hepsin is a type II serine protease that is highly expressed in neoplastic prostate. It is an attractive biomarker for imaging metastatic prostate cancer because of its overexpression in advanced prostate cancer and the location of its active site on the cell surface. We designed and synthesized novel hepsin-targeted imaging probes by conjugating the hepsin-binding ligand with near-infrared (NIR) optical dyes. The Leu-Arg dipeptides, attached to BODIPY or SulfoCy7, exhibited strong hepsin-inhibitory activities with Ki values of 21 and 22 nM, respectively. Compound 2 showed selective uptake and retention in hepsin-overexpressing cells. This is the first report of hepsin-targeted optical probes with strong binding affinities and high selectivity over matriptase. Compound 2 has the potential to be used for developing hepsin-based imaging probes and be as a prototype molecule in the design of new hepsin inhibitors. |
| Databáze: | OpenAIRE |
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