Fmoc-Diphenylalanine Self-Assembly Mechanism Induces Apparent pKa Shifts

We report the effect of pH on the self-assembly process of Fmoc-diphenylalanine (Fmoc-FF) into fibrils consisting of antiparallel beta-sheets and show that it results in two apparent pK(a) shifts of similar to 6.4 and similar to 2.2 pH units above the theoretical pK(a) (3.5). Using Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), wide angle X-ray scattering (WAXS), and oscillatory rheology, these two transitions were shown to coincide with significant structural changes. An entangled network of flexible fibrils forming a weak hydrogel dominates at high pH. while nongelling flat rigid ribbons form at intermediate pH values. Overall. this study provides further understanding of the self-assembly mechanism of aromatic short peptide derivatives.