Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation.

Autor: Bera A; Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India.; Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India., Ghosh P; Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India.; Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India., Ghosh S; Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India., Mukherjee A; Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India., De P; Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India.; Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal, 741246, India.
Jazyk: angličtina
Zdroj: Macromolecular bioscience [Macromol Biosci] 2023 Jul; Vol. 23 (7), pp. e2300100. Date of Electronic Publication: 2023 May 03.
DOI: 10.1002/mabi.202300100
Abstrakt: Lipoic acid (LA) and dihydrolipoic acid (DHLA) are well established antioxidants to scavenge reactive oxygen species (ROS). However, they are carboxylates with ≈4.7 pKa making them negatively charged at physiological pH (7.4) reducing their passive diffusion through cell membranes. LA is known to be capable of reducing protein fibrillation. Incorporation of LA and especially DHLA in polymer side chains are scarce. Herein, the first examples of the anti-amyloidogenic effect of LA and DHLA incorporated into the side-chain of a block copolymer with a water-soluble poly(polyethylene glycol methyl ether methacrylate) (PPEGMA) segment are presented. The resultant polymers show improved ROS scavenging activity and improved ability to reduce insulin fibrillation compared to free LA and DHLA. Furthermore, the resultant polymers are also capable of disintegrating preformed insulin firbrils. Interestingly, polymers with dihydro-lipoate moieties showed 93% free radical scavenging activity with 91% anti-fibrillating efficacies for insulin protein confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and Thioflavin T (ThT) dye binding study, respectively. Further, the antioxidant polymers increase the cell viability against fibrillar insulin aggregates that may be involved in the etiology of several diseases. Overall, this work reveals that antioxidant polymer-based therapeutic agents can serve as a powerful modulation strategy for developing novel drugs in future against amyloid-related disorders.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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