Ile-Phe dipeptide self-assembly: Clues to amyloid formation

Peptidic self-assembled nanostructures are said to have a wide range of applications in nanotechnology, yet the mechanistic details of hierarchical self-assembly are still poorly understood. The Phe-Phe recognition motif of the Alzheimer's A beta peptide is the smallest peptide able to assemble into higher-order structures. Here, we show that the IIe-Phe dipeptide analog is also able to self-associate in aqueous solution as a transparent, thermoreversible gel formed by a network of fibrillar nanostructures that exhibit strong birefringence upon Congo red binding. Besides, a second dipeptide Val-Phe, differing only in a methyl group from the former, is unable to self-assemble. The detailed analysis of the differential polymeric behavior of these closely related molecules provides insight into the forces triggering the first steps in self-assembly processes such as amyloid formation.