Abstract
The folding of certain proteins (e.g., enzymes) into perfectly defined 3D conformations via multi-orthogonal interactions is critical to their function. Concerning synthetic polymers chains, the “folding” of individual polymer chains at high dilution via intra-chain interactions leads to so-called single-chain nanoparticles (SCNPs). This review article describes the advances carried out in recent years in the folding of single polymer chains into discrete SCNPs via multi-orthogonal interactions using different reactive chemical species where intra-chain bonding only occurs between groups of the same species. First, we summarize results from computer simulations of multi-orthogonally folded SCNPs. Next, we comprehensively review multi-orthogonally folded SCNPs synthesized via either non-covalent bonds or covalent interactions. Finally, we conclude by summarizing recent research about multi-orthogonally folded SCNPs prepared through both reversible (dynamic) and permanent bonds.
Highlights
The compaction process of a biological linear polypeptide chain to its functional, native conformation is called protein folding [1]
This study strongly suggests that, irrespective of the number of chemical species in the chain, precursors without directional interactions cannot produce designable single-chain nanoparticles (SCNPs) but a distribution of SCNPs polydisperse in size and shape
With the long term aim of preparing macromolecules that mimic the folding actions of natural biomacromolecules, Barner-Kowollik and coworkers pioneered in 2012 the single chain folding of synthetic polymers containing two distinct and mutually orthogonal hydrogen bonding (HB) motifs: thymine (Thy)–diaminopyridine (DAP) and cyanuric acid (CA)–Hamilton wedge (HW) [55]
Summary
The compaction process of a biological linear polypeptide chain to its functional, native conformation is called protein folding [1]. Concerning synthetic polymers chains, the “folding” of individual polymer chains at high dilution via intra-chain interactions leads to so-called single-chain nanoparticles (SCNPs) [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19] In this case, the term “folding” refers to the process by which a functionalized synthetic polymer chain assumes its final shape or conformation as individual singlechain nanoparticle via non-covalent (or dynamic covalent) and/or covalent intra-chain interactions. As summarized, folding/unfolding of SCNPs has been investigated for a variety of reversible SCNPs with non-covalent bonds and dynamic covalent interactions [11], most of them involving a single interaction type (i.e., single-step crosslinking method). Spectroscopy, circular dichroism (CD) and AFM-based single-molecule force spectroscopy
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