Issue 10, 2023

Amphiphilic dendrons as supramolecular holdase chaperones

Abstract

The aggregation of incompletely or incorrectly folded proteins is implicated in diseases including Alzheimer's, cataracts, and other maladies. Natural systems express protein chaperones to prevent or even reverse harmful protein aggregation. Synthetic chaperone-like systems have sought to mimic the action of their biological counterparts but typically require substantial optimization and high concentrations to be functional, or lack programmability that would enable the targeting of specific protein substrates. Here we report a series of amphiphilic dendrons that undergo assembly and inhibit the aggregation of fragment 16–22 amyloid β protein (Aβ16–22). We show that monodisperse dendrons with hydrophilic tetraethylene glycol chains and a hydrophobic core based on naphthyl and benzyl ethers undergo supramolecular assembly in aqueous solutions to form sphere-like particles. The solubility of these dendrons and their assemblies is tuned by varying the relative sizes of their hydrophilic and hydrophobic regions. Two water-soluble dendrons are discovered and shown, via fluorescence experiments with rhodamine 6G, to generate a hydrophobic environment. Furthermore, we demonstrate that sub-stoichiometric concentrations of these amphiphilic dendrons stabilize Aβ16–22 peptide with respect to aggregation, mimicking the activity of holdase chaperones. Our results highlight the potential of these amphiphilic molecules as the basis for a novel approach to artificial chaperones that may address many of the challenges associated with existing synthetic chaperone mimics.

Graphical abstract: Amphiphilic dendrons as supramolecular holdase chaperones

Supplementary files

Article information

Article type
Communication
Submitted
06 jun 2023
Accepted
05 sep 2023
First published
08 sep 2023
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2023,4, 754-759

Amphiphilic dendrons as supramolecular holdase chaperones

E. R. Piedmont, E. E. Christensen, T. D. Krauss and B. E. Partridge, RSC Chem. Biol., 2023, 4, 754 DOI: 10.1039/D3CB00086A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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