title: A Co(III) complex cleaving soluble oligomers of h-IAPP in the presence of polymeric aggregates of h-IAPP.
abstract: 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.
authors: Department of Chemistry, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Tae Yeon
authors: TY
authors: Lee
authors: Woo Suk
authors: WS
authors: Chei
authors: Heeyeon
authors: H
authors: Ju
authors: Mi-Sook
authors: MS
authors: Lee
authors: Jung Weon
authors: JW
authors: Lee
authors: Junghun
authors: J
authors: Suh
mesh_terms: D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility
chemical_list: D056831:Coordination Complexes; D058228:Islet Amyloid Polypeptide; D003035:Cobalt