New chelating ligands for Co(III)-based peptide-cleaving catalysts selective for pathogenic proteins of amyloidoses
| Autor: | Woo Suk Chei, Heeyeon Ju, Junghun Suh |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
chemistry.chemical_classification
Amyloid Molecular Structure Stereochemistry Chemistry Proteins Peptide Amyloidosis Cleavage (embryo) Biochemistry Combinatorial chemistry Catalysis Chemical library Inorganic Chemistry chemistry.chemical_compound Amyloid disease Cleave Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Organometallic Compounds Molecule Humans Peptides Copper |
| Zdroj: | Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 16(3) |
| ISSN: | 1432-1327 |
| Popis: | The Co(III) complex of 1,4,7,10-tetraazacyclododecane has been employed as the catalytic center of target-selective peptide-cleaving catalysts in previous studies. As new chelating ligands for the Co(III) ion in the peptide-cleaving catalysts, 1-oxo-4,7,10-triazacyclodedecane, 1-aryl-1,4,7,10-tetraazacyclodecane, and 7-aryl-1-oxo-4,7,10-triazacyclodecane were examined in the present study. A chemical library comprising 612 derivatives of the Co(III) complex of the new chelating ligands was constructed. The catalyst candidates were tested for their activity to cleave the soluble oligomers of amyloidogenic peptides amyloid β-42 and human islet amyloid polypeptide (h-IAPP), which are believed to be the pathogenic species for Alzheimer's disease and type 2 diabetes mellitus, respectively. One derivative of the Co(III) complex of 1-aryl-1,4,7,10-tetraazacyclodecane was found to cleave the oligomers of h-IAPP. Cleavage products were identified and cleavage yields were measured at various catalyst concentrations for the action of the new catalyst. The present results reveal that effective catalytic drugs for amyloidoses may be obtained by using Co(III) complexes of various chelating ligands. |
| Databáze: | OpenAIRE |
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