Bottlebrush polymers with flexible enantiomeric side chains display differential biological properties.

Autor: Nguyen HV; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Jiang Y; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Mohapatra S; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Wang W; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Barnes JC; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Oldenhuis NJ; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Chen KK; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Axelrod S; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA., Huang Z; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Chen Q; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Golder MR; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Young K; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Suvlu D; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Shen Y; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Willard AP; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Hore MJA; Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH, USA., Gómez-Bombarelli R; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. rafagb@mit.edu., Johnson JA; Department of Chemistry and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. jaj2109@mit.edu.
Jazyk: angličtina
Zdroj: Nature chemistry [Nat Chem] 2022 Jan; Vol. 14 (1), pp. 85-93. Date of Electronic Publication: 2021 Nov 25.
DOI: 10.1038/s41557-021-00826-8
Abstrakt: Chirality and molecular conformation are central components of life: biological systems rely on stereospecific interactions between discrete (macro)molecular conformers, and the impacts of stereochemistry and rigidity on the properties of small molecules and biomacromolecules have been intensively studied. Nevertheless, how these features affect the properties of synthetic macromolecules has received comparably little attention. Here we leverage iterative exponential growth and ring-opening metathesis polymerization to produce water-soluble, chiral bottlebrush polymers (CBPs) from two enantiomeric pairs of macromonomers of differing rigidity. Remarkably, CBPs with conformationally flexible, mirror image side chains show several-fold differences in cytotoxicity, cell uptake, blood pharmacokinetics and liver clearance; CBPs with comparably rigid, mirror image side chains show no differences. These observations are rationalized with a simple model that correlates greater conformational freedom with enhanced chiral recognition. Altogether, this work provides routes to the synthesis of chiral nanostructured polymers and suggests key roles for stereochemistry and conformational rigidity in the design of future biomaterials.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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