β-Amyloid Targeting with Two-Dimensional Covalent Organic Frameworks : Multi-Scale In-Silico Dissection of Nano-Biointerface

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Maleki , R , Khedri , M , Rezvantalab , S , Afsharchi , F , Musaie , K , Shafiee , S & Shahbazi , M-A 2021 , ' β-Amyloid Targeting with Two-Dimensional Covalent Organic Frameworks : Multi-Scale In-Silico Dissection of Nano-Biointerface ' , ChemBioChem : a European journal of chemical biology , vol. 22 , no. 13 , pp. 2306-2318 . https://doi.org/10.1002/cbic.202100075

Title: β-Amyloid Targeting with Two-Dimensional Covalent Organic Frameworks : Multi-Scale In-Silico Dissection of Nano-Biointerface
Author: Maleki, Reza; Khedri, Mohammad; Rezvantalab, Sima; Afsharchi, Fatemeh; Musaie, Kiyan; Shafiee, Sepehr; Shahbazi, Mohammad-Ali
Contributor organization: Nanomedicines and Biomedical Engineering
Division of Pharmaceutical Chemistry and Technology
Drug Research Program
Date: 2021-07-01
Language: eng
Number of pages: 13
Belongs to series: ChemBioChem : a European journal of chemical biology
ISSN: 1439-4227
DOI: https://doi.org/10.1002/cbic.202100075
URI: http://hdl.handle.net/10138/332943
Abstract: Cytotoxic aggregation of misfolded beta-amyloid (A beta) proteins is the main culprit suspected to be behind the development of Alzheimer's disease (AD). In this study, A beta interactions with the novel two-dimensional (2D) covalent organic frameworks (COFs) as therapeutic options for avoiding beta-amyloid aggregation have been investigated. The results from multi-scale atomistic simulations suggest that amine-functionalized COFs with a large surface area (more than 1000 m(2)/gr) have the potential to prevent A beta aggregation. Gibb's free energy analysis confirmed that COFs could prevent protofibril self-assembly in addition to inhibiting beta-amyloid aggregation. Additionally, it was observed that the amine functional group and high contact area could improve the inhibitory effect of COFs on A beta aggregation and enhance the diffusivity of COFs through the blood-brain barrier (BBB). In addition, microsecond coarse-grained (CG) simulations with three hundred amyloids reveal that the presence of COFs creates instability in the structure of amyloids and consequently prevents the fibrillation. These results suggest promising applications of engineered COFs in the treatment of AD and provide a new perspective on future experimental research.
Subject: 2D materials
Alzheimer's disease
β-amyloid
covalent organic frameworks
molecular simulation
ALZHEIMERS-DISEASE
GOLD NANOPARTICLES
GRAPHENE OXIDE
ELECTRIC-FIELD
AGGREGATION
INHIBITION
PEPTIDE
NEUROTOXICITY
FIBRILLATION
CLEARANCE
318 Medical biotechnology
221 Nano-technology
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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