Affiliations: Department of Chemistry, University of Wisconsin–Madison, Madison, WI, USA
Note:  Corresponding author: Martin T. Zanni, Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, WI 53706, USA. Fax: +1 608 262 9918; E-mail: email@example.com
Abstract: Amylin is a small polypeptide that is implicated in type 2 diabetes. This article reviews the data and conclusions presented at the 2013 ECSBM meeting in Oxford about the aggregation mechanism of amylin into toxic oligomers and fibers. The process was studied using a pulse shaping method for collecting two-dimensional infrared (2D IR) spectra in order to monitor aggregation in real time. Isotope labeling was used to measure the secondary structure content of individual residues. It was found that prior to fiber formation, peptides aggregate into an intermediate that has parallel β-structure from residues 23–27, called the “FGAIL” region due to its sequence. This region has long been implicated in the aggregation process, but with confusing and often contradictory experimental results. Our work using 2D IR spectroscopy has helped reconcile these perceived contradictions and provides a mechanism that helps explain sequence homology between species, drug inhibition, and aggregation kinetics.
Keywords: Amylin, infrared spectroscopy, 2D IR, aggregation pathway, intermediate