Acid-responsive fibrillation and urease-assisted defibrillation of phenylalanine: a transient supramolecular hydrogel

Abstract

The aggregation of proteins and peptides into fibrils is associated with many neurodegenerative diseases in humans, including Alzheimer's disease, Parkinson's disease and non-neurological type-II diabetes. A better understanding of the fibril formation process and defibrillation using biochemical tools is highly important for therapeutics. Under physiological conditions, acidic pH promotes the formation of toxic fibrils. Here, a mimic of living systems has been achieved by the acid-responsive assembly of benzyloxycarbonyl-L-phenylalanine to fibrils, as well as the urease-assisted disassembly of the said fibrils. The simultaneous incorporation of the two triggers helped to prepare a transient supramolecular hydrogel from benzyloxycarbonyl-L-phenylalanine-entangled fibrils with a high degree of control over the self-assembly lifetime and mechanical properties. Further, under acidic pH, the compound formed the O–H⋯OC hydrogen-bonded dimer. The dimers were further self-assembled by intermolecular N–H⋯OC hydrogen bonds and π–π stacking interactions to form fibrils with high mechanical properties, from this simple molecule. However, the self-assembly process is dynamic. Hence, the in situ-generated NH₃ uniformly increased the pH and led to the homogeneous disassembly of the fibrils. Thus, this report provides a valuable approach to defibrillation.