Abstract
Dynamic protein assembly along supramolecular columnar polymers has been achieved through the site-specific covalent attachment of different SNAP-tag fusion proteins to self-assembled benzylguanine-decorated discotics. The self-assembly of monovalent discotics into supramolecular polymers creates a multivalent, bio-orthogonal and self-regulating framework for protein assembly. The intrinsic reversibility of supramolecular interactions results in reorganization and exchange of building blocks allowing for dynamic intermixing of protein-functionalized discotics between different self-assembled polymers, leading to self-optimization of protein arrangement and distance as evidenced by efficient energy transfer between fluorescent proteins.
Highlights
The assembly of proteins in cells and on cell membranes is essential for a diverse range of fundamental biological processes including gene transcription, signal transduction and the regulation of metabolic pathways.[1,2,3] The underlying design principles of these natural protein assemblies such as wellde ned spatial organization and shape, induced proximity, and multivalency have inspired the design of synthetic scaffolds for protein assembly based on small molecules,[4,5,6,7] dendrimers,[8,9,10] and natural and synthetic polymers,[11,12,13,14,15,16,17] which exemplify many of these bene cial features with applications in diagnostics and nanotechnology
A discotic supramolecular building block monofunctionalized with O6-benzylguanine (2), a reactive functionality for bio-orthogonal protein conjugation, was designed, offering a non-sterically hindered general platform for the covalent attachment of diverse proteins
The distance between the proteins and with it the decrease in FRET ratio could be tuned via the addition of different concentrations of 3. These results show that in contrast to the typically applied strategy for the generation of heterovalent supramolecular polymers – pre-mixing different building blocks prior to self-assembly40,41 – heterovalent structures based on discotics can as well be formed and ne-tuned a er selfassembly. This proof-of-principle work using uorescent proteins as model proteins showed the possibility to generate adaptable, hetero- and multivalent protein assemblies using supramolecular polymers based on monovalent discotics
Summary
The assembly of proteins in cells and on cell membranes is essential for a diverse range of fundamental biological processes including gene transcription, signal transduction and the regulation of metabolic pathways.[1,2,3] The underlying design principles of these natural protein assemblies such as wellde ned spatial organization and shape, induced proximity, and multivalency have inspired the design of synthetic scaffolds for protein assembly based on small molecules,[4,5,6,7] dendrimers,[8,9,10] and natural and synthetic polymers,[11,12,13,14,15,16,17] which exemplify many of these bene cial features with applications in diagnostics and nanotechnology. The intrinsic reversibility of supramolecular interactions results in reorganization and exchange of building blocks allowing for dynamic intermixing of protein-functionalized discotics between different self-assembled polymers, leading to self-optimization of protein arrangement and distance as evidenced by efficient energy transfer between fluorescent proteins. We present the site-speci c, bio-orthogonal, and covalent conjugation of single proteins to an intrinsically monovalent discotic molecule functionalized with one O6-benzylguanine moiety (Fig. 1a).
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