Protein‐Inspired Control over Synthetic Polymer Folding for Structured Functional Nanoparticles in Water

Abstract

The folding of proteins into functional nanoparticles with defined 3D structures has inspired chemists to create simple synthetic systems mimicking protein properties. The folding of polymers into nanoparticles in water proceeds via different strategies, resulting in the global compaction of the polymer chain. Herein, we review the different methods available to control the conformation of synthetic polymers and collapse/fold them into structured, functional nanoparticles, such as hydrophobic collapse, supramolecular self‐assembly, and covalent cross‐linking. A comparison is made between the design principles of protein folding to synthetic polymer folding and the formation of structured nanocompartments in water, highlighting similarities and differences in design and function. We also focus on the importance of structure for functional stability and diverse applications in complex media and cellular environments.

Tailoring Hierarchical Structure and Rare Earth Affinity of Compositionally Identical Polymers via Sequence Control

“…SCPs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were synthesized via iterative reversible addition−fragmentation transfer (RAFT) polymerizations to achieve blocky copolymers with controlled molecular weights and low Đ (Tables 1 and S1 and Schemes S2 and S3). 15 As ≥90% of the added monomer was consumed before subsequent block extension, leaving at most one monomer unincorporated, no intermediate purification steps were performed (Tables S2−S4).…”

“…35,36 While polymeric materials offer tunable multivalent interactions, current designs lack the tailored structures required for substrate selectivity and affinity. [2][3][4]37 Drawing inspiration from biological systems, we sought to connect facets of the polymer structure at multiple length scales. To achieve this, we leveraged multiblock polymerization, strategically biasing the location of monomers along the chain to generate ensembles of polymers that are a subset of a statistical polymer distribution featuring domains (i.e., patches) with higher frequencies of specific monomers.…”

“…Proteins are exemplary of the intricate relationship between the structure and function of macromoleculesprecision folding governed by sequence patterning of amino acids enables efficient catalysts and receptors in complex aqueous environments . The sophisticated capabilities of proteins have spurred efforts to translate their functionality into synthetic polymers, which offer expanded monomer chemistries and stability for use as enzyme mimics, multivalent therapeutics, and sequestrants for contaminants and valuable materials. − Decades of synthetic development have enabled control over polymer primary structure, including composition, molecular weight, and monomer patterning. , Additionally, the integration of structure at ligand-relevant length scales, akin to secondary structure, has been achieved with motifs incorporated into monomers: benzene-1,3,5-carboxamide that forms helical structures and di­(phenylalanine) (FF) that elicits solvent segregated β-sheet-like interactions. , However, the complex hierarchical structures of proteins have yet to be achieved with synthetic systems, which has limited their functional performance.…”

Einzelkettennanopartikel in der Katalyse

“…[40] Es ist daher von entscheidender Bedeutung, die interne Morphologie von EKNPs für die Katalyse zu bestimmen, um herauszufinden, wie sich die morphologischen Veränderungen in EKNPs auf ihre katalytische Aktivität auswirken. Obwohl bereits mehrere Übersichtsartikel existieren, welche die Fortschritte in der EKNP-Technologie und -Katalyse zusammenfassen, [20,23,40,[43][44][45][46][47][48][49][50][51][52][53][54] hat es in den letzten Jahren zahlreiche Fortschritte in der auf EKNP basierenden Katalyse gegeben. Allerdings gibt es keine Übersicht über die neuesten Erkenntnisse, so dass wir in diesem Beitrag diese Lücke in der Literatur schließen.…”

pH‐Controlled Reversible Folding of Copolymers via Formation of β‐sheet Secondary Structures

“…Consequently, many attempts have been made to develop synthetic polymer materials with the same degree of structural organization. Controlled folding of polymer chains of different natures has been achieved through a variety of intramolecular cross-linking strategies, exploiting both covalent and non-covalent interactions of side chains or chain ends, [1][2][3] and found numerous applications. [4][5][6][7][8][9] However, the control over polymer folding achieved to date does not reach the degree of complexity of intramolecular interactions displayed by proteins, with the undefined primary sequence of conventional synthetic polymers and their all-carbon backbones being key limitations.…”