Peptide Undergoes 'Jekyll-Hyde' Mutation

A single mutation has been found to convert the function of a peptide in a "Jekyll and Hyde" manner&mdsh;from a version that forms toxic amyloid fibrils to another that inhibits amyloid formation. In type 2 diabetes patients, islet amyloid polypeptide (amylin) forms amyloid fibrils that are believed to contribute to the loss of insulin-producing pancreatic β-cells and progression of the disease. Andisheh Abedini, Fanling Meng, and Daniel P. Raleigh at the State University of New York, Stony Brook, now find that a single point mutation converts amylin from one of the most aggregation-prone peptides known into a potent inhibitor of amyloid formation (J. Am. Chem. Soc. 2007, 129, 11300). Because mutated amylin retains binding affinity to natural amylin, the agent combines target recognition with aggregation-disrupting ability and thus represents a possible lead for the development of antidiabetic drugs. Indeed, an amylin analog has already been approved by FDA and is on the market for treatment of type 1 diabetes, Raleigh notes.