Self-Adaptive Synthesis of Non-Covalent Crosslinkers while Folding Single-Chain Polymers

Loading...
Thumbnail Image

Access rights

openAccess

URL

Journal Title

Journal ISSN

Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2024-09-16

Major/Subject

Mcode

Degree programme

Language

en

Pages

Series

Angewandte Chemie - International Edition, Volume 63, issue 38

Abstract

Peptide folding is a dynamic process driven by non-covalent cross-linking leading to functional nanostructures for essential biochemical activities. However, replicating this process in synthetic systems is challenging due to the difficulty in mimicking nature‘s real-time regulation of non-covalent crosslinking for single-chain polymer folding. Here, we address this by employing anionic dithiol building blocks to create macrocyclic disulfides as non-covalent crosslinkers that adapted to the folding process. Initially, small macrocycles facilitated a low degree folding of a polycation. Then, this preorganized structure catalysed the production of larger macrocycles that enhanced the folding conversely. The self-adaptive synthesis was verified through the encapsulation of an anticancer drug, showing an updated production distribution of non-covalent crosslinkers and maximizing drug-loading efficiency against drug-resistant cancer in vitro. Our research advances the understanding of molecular systems by exploring species evolution via the structural dynamics of polymer folding. Additionally, adaptive synthesis enables controlled, sequential folding of synthetic polymers, with the potential to mimic protein functions.

Description

Publisher Copyright: © 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Keywords

dynamic combinatorial chemistry, polymer folding, single-chain nanoparticle, supramolecular chemistry

Other note

Citation

Qi, D, Shi, X, Lin, C, Holzhausen, F, Ville, L, Sun, X, Luo, J, Pitkänen, L, Zhu, Y, Rosenholm, J, Jalkanen, S & Li, J 2024, ' Self-Adaptive Synthesis of Non-Covalent Crosslinkers while Folding Single-Chain Polymers ', Angewandte Chemie - International Edition, vol. 63, no. 38, e202408670 . https://doi.org/10.1002/anie.202408670