Acid-responsive fibrillation and urease-assisted defibrillation of phenylalanine: a transient supramolecular hydrogel
Sahabaj Mondal, Debasish Podder, Sujay Kumar Nandi, Srayoshi Roy Chowdhury, Debasish Haldar
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-HO[double bond, length as m-dash]C hydrogen-bonded dimer. The dimers were further self-assembled by intermolecular N-HO[double bond, length as m-dash]C 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.