Inhibition of human and bovine insulin fibril formation by designed peptide conjugates.

The aggregation of insulin, to afford amyloidogenic fibers, is a well-studied phenomenon, which has interesting biological ramifications and pharmaceutical implications. These fibers have been ascribed an intriguing role in certain disease states and stability of pharmaceutical formulations of this hormone. The present study describes the design and inhibitory effects of novel peptide conjugates toward fibrillation of insulin as investigated by thioflavin T assay, circular dichroism (CD), and atomic force microscopy (AFM). Possible interaction of insulin with peptide-based fibrillation inhibitors is also probed by other solution phase studies, which reveal an important role of aromatic π-π interactions in the inhibition process. CD studies suggest that a freshly prepared solution of insulin, rich in α-helices, transforms into a β-sheet structure upon aggregation, which gets perturbed in the presence of synthesized inhibitors. Therefore, these newly designed peptides could serve as potential leads as inhibitors of insulin aggregation.