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

Authors

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

Conference / event

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

Poster summary

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.

Keywords

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

Research areas

Neuroscience, Molecular and Cellular Biosciences, Biological Sciences

References

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Funding

No data provided

Supplemental files

1. Published Manuscript   Download
2. Supporting Information_Manuscript   Download

Additional information

Competing interests

No competing interests were disclosed.

Data availability statement

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

Creative Commons license

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.