A Co(III) complex cleaving soluble oligomers of h-IAPP in the presence of polymeric aggregates of h-IAPP

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.