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

• Published in: Soft matter 2020-11, Vol.16 (44), p.1115-1121
• Main Authors: Mondal, Sahabaj, Podder, Debasish, Nandi, Sujay Kumar, Roy Chowdhury, Srayoshi, Haldar, Debasish
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Ammonia; Diabetes mellitus; Dimers; Dismantling; Fibrillation; Fibrillogenesis; Hydrogels; Hydrogen bonding; Hydrogen bonds; Mechanical properties; Movement disorders; Neurodegenerative diseases; Parkinson's disease; Peptides; pH effects; Phenylalanine; Self-assembly; Urease
• ISSN: 1744-683X; 1744-6848
• DOI: 10.1039/d0sm00774a

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 O&z.dbd;C hydrogen-bonded dimer. The dimers were further self-assembled by intermolecular N-H O&z.dbd;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 NH 3 uniformly increased the pH and led to the homogeneous disassembly of the fibrils. Thus, this report provides a valuable approach to defibrillation. A mimic of living systems has been achieved by the acid-responsive assembly and urease-assisted disassembly of fibrils from benzyloxycarbonyl- l -phenylalanine, leading to a transient supramolecular hydrogel.