Deciphering the self-assembly mechanisms of three diphenylalanine derivatives using infrared probe technique and...

Understanding the nucleation mechanism of peptide self-assembly is fundamental for the design and application of peptide-based materials. To this end, we herein explored the self-assembly processes of three diphenylalanine (FF) derivatives, Boc-XF, Boc-FX, and Boc-FF, where X is p-cyanophenylalanine with the cyano group being an infrared (IR) probe. Using IR probe technique and scanning electron microscopy (SEM), we revealed that the self-assembly of Boc-XF followed a three-step non-classical nucleation mechanism. Such a complex mechanism involved the presence of metastable spherical and fibrillar intermediates towards the final mature fibril phase. We further compared the self-assembly mechanism of Boc-XF with that of Boc-FF and Boc-FX and explored the potential impact of side-chain mutation on the peptide self-assembly mechanism. Our research provided a nice example of how to use a combined approach of IR probe technique and SEM to reveal the complex nucleation mechanism of peptide self-assembly.