Exploring and Controlling the Polymorphism in Supramolecular Assemblies of Carbohydrates and Proteins

In biology, polymorphism is a well-known phenomenon by which a discrete biomacromolecule can adopt multiple specific conformations in response to its environment. This term can be extended to the ability of biomacromolecules to pack into different ordered patterns. Thus, exploration and control of the polymorphism of biomacromolecules via supramolecular methods have been key steps in achieving bioinspired structures, developing bioinspired functional materials, and exploring the mechanisms of these self-assembly processes, which are models for more complex biological systems. This task could be difficult for proteins and carbohydrates due to the complicated multiple noncovalent interactions of these two species which can hardly be manipulated.In this account, dealing with the structural polymorphisms from biomacromolecular assemblies, we will first briefly comment on the problems that carbohydrate/protein assemblies are facing, and then on the basis of our long-term research on carbohydrate self-assemblies, we will summarize the new strategies that we have developed in our laboratory in recent years to explore and control the polymorphism of carbohydrate/protein assemblies.Considering the inherent ability of carbohydrates to recognize lectin, we proposed the "inducing ligand" strategy to assemble natural proteins into various nanostructures with highly ordered packing patterns. The newly developed inducing ligand approach opened a new window for protein assembly where dual noncovalent interactions (i.e., carbohydrate-protein interactions and dimerization of rhodamine) instead of the traditionally used protein-protein interactions direct the assembly pattern of proteins. As a result, various polymorphisms of protein assemblies have been constructed by simply changing the ligand chemical structure and/or the rhodamine dimerization.Another concept that we proposed for glycopolymer self-assembly is DISA (i.e., deprotection-induced glycopolymer self-assembly). It is well known that protection-deprotection chemistry has been employed to construct complex oligosaccharide structures. However, its application in glycopolymer self-assembly has been overlooked. We initiated this new strategy with diblock copolymers. Such copolymers with a carbohydrate block having protected pendent groups exist as single chains in organic media. The self-assembly can be initiated by the deprotection of the pendent groups. The process was nicely controlled by introducing various protective groups with different deprotection rates. Later on, the DISA process has been proven practical in water and even in the cellular environment, which opens a new avenue for the development of polymeric glycomaterials.Finally, the resultant polymeric glyco-materials, as a new type of biomimetic materials, provide a nice platform for investigating the functions of glycocalyx. The glycocalyx-mimicking nanoparticles achieved unprecedent functions which exceed their carbohydrate precursors. Here, the reversion of tumor-associated macrophages induced by glycocalyx-mimicking nanoparticles will be discussed with potential applications in cancer immunotherapy, where such a reversion effect could be combined with other methods (e.g., tumor checkpoint blockade).