TY - JOUR
T1 - Self-Adaptive Synthesis of Non-Covalent Crosslinkers while Folding Single-Chain Polymers
AU - Qi, Dawei
AU - Shi, Xuncheng
AU - Lin, Caihong
AU - Holzhausen, Ferdinand
AU - Ville, Liljeström
AU - Sun, Xun
AU - Luo, Jinghui
AU - Pitkänen, Leena
AU - Zhu, Ya
AU - Rosenholm, Jessica
AU - Jalkanen, Sirpa
AU - Li, Jianwei
PY - 2024/9/16
Y1 - 2024/9/16
N2 - 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.
AB - 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.
KW - dynamic combinatorial chemistry
KW - supramolecular chemistry
KW - polymer folding
KW - single-chain nanoparticle
U2 - 10.1002/ange.202408670
DO - 10.1002/ange.202408670
M3 - Article
SN - 1433-7851
VL - 136
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
IS - 38
M1 - e202408670
ER -