A side-chain tripeptide based PEGylated block copolymer: a potential drug candidate in Alzheimer’s disease translational therapeutics

作者

Sutapa Som Chaudhury¹ , Jaya Sil¹ , Sabyashachi Mishra² , Chitrangada Das Mukhopadhyay¹

1. Indian Institute of Engineering Science and Technology, Shibpur
2. Indian Institute of Technology, Kharagpur

会议/活动

4th IBRO/APRC Chandigarh Associate Neuroscience School, November 2019 (Chandigarh, India)

海报摘要

Despite a 100 years of research in Alzheimer’s disease (AD), there is no therapeutic measure available till date for AD. The researchers here have designed and synthesized a PEGylated, side-chain tripeptide (leu-val-phe) based block copolymer targeting anti- aggregation of misfolded amyloid beta peptide (Aβ1-42). The block copolymer was assessed via different in vitro and in silico techniques e.g., thioflavin T (ThT) assay, dynamic light scattering (DLS) analyses, atomic force microscopy (AFM), electron microscopy, and molecular dynamic (MD) simulation techniques. A significant demolition of the characteristic β- sheet structure of growing Aβ42 fibril chain in presence of the inhibitor was observed through their experiments. Also, they deciphered the drug mechanism of action as a competitive inhibition between the hydrophobic core region of Aβ42 and the block copolymer itself. Thus, the researchers showed the PEGylated block copolymer as a promising drug candidate of AD.

关键词

Alzheimer's disease, Amyloid beta peptide, Inhibitor, Fibrillization, Peptidomimetics, MD simulation

研究领域

Neuroscience, Molecular and Cellular Biosciences, Biological Sciences

参考文献

1. S Som Chaudhury, A Sannigrahi, M Nandi, V K Mishra, P De, K Chattopadhyay, S Mishra, J Sil and C Das Mukhopadhyay, Molecular Neurobiology 56, 2019, 6551–6565.
2. H Xu, J Park, W Wu, A Malagon, L Wang, E Vargas, A Wikramanayake, K N Houk and R M Leblanc, Chemical science 8, 2017, 2003-2009.
3. C D Mukhopadhyay, B Ruidas and S S Chaudhury, Int J Neurorehabilitation 4, 2017, 2376-0281.
4. S Hadas, R Chen, I Grinberg and S Margel, Biomacromolecules 13, 2012, 2662-2670.
5. B Sergey O, E V Bovina and A A Ustyugov, Medicinal research reviews 37, 2017, 1186-1225.
6. J L Cummings, T Morstorf and Kate Zhong, Alzheimer's research & therapy 6, 2014, 37.
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基金

暂无数据

补充材料

1. Published Manuscript   Download
2. Supporting Information_Manuscript   Download

附加信息

利益冲突

No competing interests were disclosed.

数据可用性声明

The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.

知识共享许可协议

Copyright © 2023 Som Chaudhury et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.