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Modulation of phenylalanine assembly kinetics by gallic acid and its therapeutic implications in phenylketonuria
Talat Zahra1, Nabodita Sinha1, Ashwani Kumar Thakur1
1Department of Biological Sciences and Bioengineering, The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh-208016, India. akthakur@iitk.ac.in.
Abstract:
Self-assembly of L-phenylalanine (Phe) results in the formation of assemblies that are structurally and functionally related to amyloid-like fibrils. Recently, Phe assembly has been correlated with the elevated Phe levels observed in phenylketonuria (PKU) patients. The presence of Phe aggregates in the post-mortem brain sections of PKU patients and in transgenic mouse models suggests their plausible role in disease pathology. To inhibit Phe assembly, we hypothesized that gallic acid (GA), a known antioxidant, could interfere with the assembly process owing to its generic anti-amyloid activity. Here, using multiple biophysical techniques, we demonstrate the characteristic features of Phe assembly and its disassembly in the presence of GA. Owing to its natural occurrence in plants and its therapeutic potential, GA may serve as a promising molecule for future preclinical testing in PKU mouse models.
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