Seaver News

Moffett Publishes Article

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Faculty Achievements

Ayano Fox, Thibaut Snollaerts, Camille Errecart Casanova, Anastasia Calciano, Luiza A. Nogaj and David A. Moffet (2010) Selection for Nonamyloidogenic Mutants of Islet Amyloid Polypeptide (IAPP) Identifies an Extended Region for Amyloidogenicity. Biochemistry 49: 7783-7789.

The small peptide, IAPP, is a naturally occurring protein that is co-secreted with insulin in the pancreas. In type II diabetes, it has been shown that IAPP peptides aggregate together. This aggregation leads to the formation of toxic amyloid, which is known to kill pancreatic β-cells. While it has been known for some time that IAPP aggregates into toxic amyloid, no one had experimentally identified the aggregation-prone region(s) of this peptide. My students and I were able to identify the aggregation-prone regions of IAPP. Our results showed that two regions exist that are important for this aggregation. One of these regions was expected and has been considered the “aggregation prone region” of IAPP for several years. However, we discovered a second region of the protein that is also a major contributor to the aggregation event. Knowing that both regions play a role in aggregation may lead us to developing drugs that can prevent IAPP aggregation and possibly slow (if not stop) the progression of type II diabetes.

Note: Ayano and Anastasia, coauthors on the above article, spent much of summer 2010 designing compounds targeting both aggregation prone regions of IAPP with the hope of discovering therapeutically active agents. The team hopes to produce more on the subject in the coming months!