Research
The Niu group conducts interdisciplinary research spanning materials science and chemical biology, with the overarching theme of creating precision functional macromolecules tailored for material, biological, and sustainability applications. We consider āmacromoleculesā broadly defined to include synthetic polymers, biopolymers, and anything in between (e.g., biomimetic synthetic polymers, non-natural biopolymers, etc.). Various strategies including rational design and directed evolution are implemented in the following three main directions:
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Precision Polymers and Biopolymers
Polymers have fundamentally changed our society, but have also caused significant issues ranging from pollution to toxicity. A long-term goal of our research is to develop new technologies for the synthesis of polymers and biopolymers (in particular polysaccharides) with defined molecular weight, side chain modifications, and chain-end structures. Our contribution to this field are as follows: (1) We established a novel strategy for incorporating degradable motifs into non-degradable vinyl polymers through radical ring-opening cascade (co)polymerization (JACS 2018, JACS 2019, Macromolecules 2020, Angew. Chem. 2021, Angew. Chem. 2022, ACS Cent. Sci. 2023, Macromolecules 2023, JACS 2024). (2) We generated a new class of enyne self-immolative polymers that are stable under harsh conditions (e.g., strong acid/base/nucleophile, high temperature, etc.), but can undergo efficient depolymerization when triggered by metathesis catalysts (Angew. Chem. 2021). (3) We developed a living cationic polymerization approach to synthesizing precision polysaccharides with well-controlled molecular weight, low dispersity, and defined chain-end groups (Nat. Chem. 2023, JACS 2024).
ChemicalTools to Study Carbohydrate and Protein Sulfation
Sulfation plays a central role in many biological processes among proteins and carbohydrates, but their functional roles are not fully understood due to the highly heterogenicity of the sulfated biomolecules. A long-term goal of our group is to develop chemical tools for probing the functional roles of sulfation in biology. Our contributions to this field are as follows: (1) Capitalizing on the sulfur (VI) fluoride exchange (SuFEx) reaction, we established strategies for controlling macromolecular sequence and for installing sulfate diesters as ālatent sulfatesā in the early stage of the synthesis (Angew. Chem. 2020, ACS Macro Lett. 2021). (2) We developed a series of disaccharide building blocks that can be quickly assembled into sequence-defined polymers with defined sulfation patterns (Angew. Chem. 2018, Chem. Sci. 2023). (3) We developed a novel method to introduce "latent "sulfates in peptides and proteins and unmask them under physiologically relevant conditions and/or in a spatiotemporally controlled manner (JACS 2023)
Functional Nucleic Acids
Nucleic acids have emerged as a new class of functional materials in a wide range of diagnostic and therapeutic applications beyond carrying genetic information. As sequence-defined polymers, nucleic acids possess unique advantages such as ease of amplification, predictable thermal properties, programmable three-dimensional folding, and well-established technologies for their intracellular trafficking. We are interested in developing next-generation nucleic acid polymers for advanced applications in biomedicine, such as immunomodulation and genome editing. Specifically, our research in this area is focused on two directions: the development of aptamer-integrated genome editing systems (Cell Chem. Biol. 2021, Curr. Opin. Chem. Biol. 2021) and functional xenobiotic nucleic acid aptamers for cell surface receptors (ACS Chem. Biol. 2019, Chem. Sci. 2022).
