Screening and Identification of mutated IAPP sequences that inhibit the aggregation of human IAPP
Authors:Pius Chee, Marissa Paterson
Mentor:David Moffet, Associate Professor of Chemistry and Biochemistry, Loyola Marymount University
Islet Amyloid Polypeptide (IAPP) is a 37 amino acid peptide co-secreted with insulin by pancreatic β-cells. It is found to form amyloid plaques in >90% of people suffering from type 2 diabetes. IAPP appears to aggregate into several different species, including toxic oligomers and less toxic fibers and plaques. It is believed that substances that can prevent the aggregation of IAPP could slow, if not halt altogether, the progression of type 2 diabetes. We have constructed a library of mutated IAPP variants using random-mutagenesis PCR. This library has been screened using an IAPP-EGFP screen developed in our lab to identify those mutated IAPP sequences capable of inhibiting the aggregation of human IAPP. We have identified several IAPP mutations that appear to inhibit the aggregation of human IAPP.