A Co(III) complex cleaving soluble oligomers of h-IAPP in the presence of polymeric aggregates of h-IAPP
| Autor: | Heeyeon Ju, Tae Yeon Lee, Woo Suk Chei, Jung Weon Lee, Junghun Suh, Mi-Sook Lee |
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| Rok vydání: | 2012 |
| Předmět: |
endocrine system
Amyloid Cell Survival Clinical Biochemistry Cell Pharmaceutical Science Apoptosis Biochemistry Cell Line Chemical library chemistry.chemical_compound Amyloid disease Low affinity Coordination Complexes Insulin-Secreting Cells Cleave Drug Discovery medicine Humans Molecular Biology geography geography.geographical_feature_category Organic Chemistry Amyloidosis Cobalt Islet Combinatorial chemistry Islet Amyloid Polypeptide medicine.anatomical_structure Diabetes Mellitus Type 2 Solubility chemistry Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:5689-5693 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2012.06.089 |
| Popis: | Soluble oligomers of human islet amyloid polypeptide (h-IAPP) are believed to be the pathogenic species for type 2 diabetes mellitus. In search of the peptide-cleavage agent cleaving oligomers of h-IAPP with low affinity for polymeric aggregates of h-IAPP, a chemical library was constructed by using the Ugi condensation. From the library, a Co(III) complex was discovered to cleave soluble oligomers of h-IAPP in the presence of polymeric aggregates of h-IAPP without being captured by the aggregates considerably. The peptide-cleavage agent inhibited apoptosis of INS-1 cell by h-IAPP even in the presence of preformed polymeric aggregates of h-IAPP. This suggests that target-selective peptide-cleavage agents may be applied clinically not only to diabetes but also to various other amyloid diseases. |
| Databáze: | OpenAIRE |
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