Amyloid inspired single amino acid (phenylalanine)-based supramolecular functional assemblies: from disease to device applications.

Pandeeswar Makam, Om Shanker Tiwari, Ehud Gazit, Subrat Vishwakarma, Ruchi Shukla

Journal: Chemical Society reviews 2025;54(1):465-483

PMID: 39585081

Abstract

In the evolving landscape of biomolecular supramolecular chemistry, recent studies on phenylalanine (Phe) have revealed important insights into the versatile nature of this essential aromatic amino acid. Phe can spontaneously self-assemble into fibrils with amyloid-like properties linked to the neurological disorder phenylketonuria (PKU). Apart from its pathological implications, Phe also displays complex phase behavior and can undergo structural changes in response to external stimuli. Its ability to co-assemble with other amino acids opens up new possibilities for studying biomolecular interactions. Furthermore, Phe's coordination with metal ions has led to the development of enzyme-mimicking catalytic systems for applications in organic chemistry, environmental monitoring, and healthcare. Research on L and D enantiomers of Phe, particularly on bio-MOFs, has highlighted their potential in advanced technologies, including bioelectronic devices. This review provides a comprehensive overview of the advancements in Phe-based supramolecular assemblies, emphasizing their interdisciplinary relevance. The Phe assemblies show great potential for future therapeutic and functional biomaterial developments, from disease treatments to innovations in bionanozymes and bioelectronics. This review presents a compelling case for the ongoing exploration of Phe's biomolecular supramolecular chemistry as a fundamental framework for developing sustainable and efficient methodologies across various scientific disciplines.

Address: Department of Chemistry, Indian Institute of Technology (BHU), Varanasi, UP, 221005, India. [email protected].; The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.; The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel. [email protected].

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