Inhibition of amyloid fibrillation of single amino acid tryptophan by tannic acid: An insight into targeted therapy of hypertryptophanemia disorder

• Published in: Journal of photochemistry and photobiology. A, Chemistry. Chemistry., 2024-08, Vol.453, p.115660, Article 115660
• Main Authors: Nandy, Tonima, Biswas, Ranjit
• Format: Article
• Language: English
• Subjects: Fibril; Fluorescence; Inhibitor; Microscopy; Streak camera
• ISSN: 1010-6030; 1873-2666
• DOI: 10.1016/j.jphotochem.2024.115660

[Display omitted] •Amyloid fibrillation of single amino acid tryptophan causes hypertryptophanemia disorder.•Tannic acid (TA) is a potent inhibitor of tryptophan fibrillation.•Microscopic images show TA-induced disruption of long tryptophan fibrils.•TA hinders the formation and stability of tryptophan fibrils.•Thermodynamic analyses provide binding constant between Tryptophan and TA. Amyloid fibrillation involving specific amino acids is a key factor contributing to the development of various neurodegenerative disorders, which remain being investigated. A promising therapeutic approach for treatment involves the use of small molecules to inhibit this amyloid fibrillation. In this study, we present experimental evidence demonstrating the efficacy of tannic acid (TA) as a potent inhibitor of fibrillation, particularly in the case of the single amino acid tryptophan (Trp), which is associated with hypertryptophanemia disorder. To investigate the kinetics of fibril formation and its suppression by TA, we have employed a combination of steady-state and time-resolved fluorescence measurements. These techniques have allowed us to monitor changes in the intrinsic fluorescence of Trp and an amyloid-specific fluorophore over time. To visualize the effects of TA on Trp fibrils, we have employed various imaging techniques such as, atomic force microscopy, transmission electron microscopy, and field emission scanning electron microscopy. These imaging techniques have vividly captured the TA-induced disruption of long Trp fibrils. Dynamic light scattering measurements have complemented these microscopic observations, further supporting the notion that TA effectively hinders the formation and stability of Trp fibrils. Additionally, we have determined the binding constant and calculated changes in the free energy associated with Trp-TA interactions through temperature-dependent spectroscopic measurements. These thermodynamic analyses provide valuable insights into the underlying mechanisms of TA-induced disaggregation of larger Trp fibrils.