Soluble oligomers of amyloid �-42 peptide (A�42), a 42-mer oligopeptide, and human islet amyloid polypeptide (h-IAPP), a 37-mer oligopeptide, are implicated as the pathogenic species in amyloid diseases such as Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), respectively. Cleavage of A�42 or h-IAPP included in an oligomer may provide a novel method for reduction of A�42 or h-IAPP oligomers, offering a new therapeutic option for AD or T2DM. We have designed artificial metalloproteases for hydrolytic peptide-cleavage of oligomers of A�42 or h-IAPP by using Co(III)-cyclen as the catalytic center. From various combinatorial libraries of Co(III)-cyclen derivatives, we identified several compounds that effectively cleaved the soluble oligomers of A�42 or h-IAPP. We demonstrated that the Co(III)-cyclen derivatives readily penetrated animal cells. Recently, we succeeded to identify a compound that inhibited apoptosis of INS-1 cell, cancer of � cell, by h-IAPP even in the presence of preformed polymeric aggregates of h-IAPP.

Artificial metalloproteases based on Co(III)-cyclen as a new therapeutic option for amyloid diseases

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.