Synthesis of RNA-Amphiphiles via Atom Transfer Radical Polymerization in the Organic Phase

Jaepil Jeong; Grzegorz Szczepaniak; Subha R Das; Krzysztof Matyjaszewski

doi:10.1021/prechem.3c00042

Synthesis of RNA-Amphiphiles via Atom Transfer Radical Polymerization in the Organic Phase

Precis Chem. 2023 May 31;1(5):326-331. doi: 10.1021/prechem.3c00042. eCollection 2023 Jul 24.

Authors

Jaepil Jeong^{1

2}, Grzegorz Szczepaniak^{1

3}, Subha R Das^{1

2}, Krzysztof Matyjaszewski¹

Affiliations

¹ Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
² Center for Nucleic Acids Science & Technology, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
³ University of Warsaw, Faculty of Chemistry, Pasteura 1, 02-093 Warsaw, Poland.

Abstract

The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles, vesicles, nanosheets, and worms. Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2'-hydroxyl groups in the solid phase using an oligonucleotide synthesizer. The protecting groups successfully solubilized the RNA macroinitiator, enabling atom transfer radical polymerization (ATRP) of hydrophobic monomers. As a result, the RNA-polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage. In addition, we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA. We envision that this methodology will expand the field of RNA-polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.