RNA-Polymer Hybrids via Direct and Site-Selective Acylation with the ATRP Initiator and Photoinduced Polymerization

Abstract

Combining synthetic polymers with RNA paves the way for creating RNA-based materials with non-canonical functions. We have developed an acylation reagent that allows for direct incorporation of the atom transfer radical polymerization (ATRP) initiator into both short synthetic oligoribonucleotides and natural biomass RNA extracted from torula yeast. The acylation was performed in a quantitative yield. The resulting initiator-functionalized RNAs were used for grafting polymer chains from the RNA by photoinduced ATRP, resulting in RNA-polymer hybrids with narrow molecular weight distributions. The RNA initiator was used for the polymerization of oligo(ethylene oxide) methyl ether methacrylate, poly(ethylene glycol) dimethacrylate, and N-isopropylacrylamide monomers, resulting in RNA bottlebrushes, hydrogels, and stimuli-responsive materials. This approach, readily applicable to both post-synthetic and nature-derived RNA, can be used to engineer the properties of a variety of RNA-based macromolecular hybrids and assemblies providing access to a wide variety of RNA-polymer hybrids.

Red-Light-Driven Atom Transfer Radical Polymerization for High-Throughput Polymer Synthesis in Open Air

“…Aqueous photo-RDRP can be used to prepare well-defined bioconjugates for biomedical applications. ,, Since nucleic acids have negligible absorption in the red light range, we attempted to synthesize DNA-based bioconjugates using MB + /Cu-catalyzed photo-ATRP. To test the feasibility of this mild dual-catalytic system in the synthesis of biohybrids, we prepared a DNA–polymer bioconjugate by the “grafting-from” approach (Figure ).…”

“…To test the feasibility of this mild dual-catalytic system in the synthesis of biohybrids, we prepared a DNA–polymer bioconjugate by the “grafting-from” approach (Figure ). − DNA functionalized with a single ATRP initiator at the 5′ terminal (T 10 -Br) was synthesized as previously reported , and then used for chain extension with the hydrophilic OEOMA 500 under the optimized conditions using the molar ratio [OEOMA 500 ]/[T 10 -Br]/[MB + ]/[CuBr 2 ]/[TPMA] = 400/1/0.05/0.6/1.8. After 30 min of red light irradiation, a well-defined bioconjugate (DNA- b -pOEOMA 500 ) was obtained with 76% monomer conversion, excellent correlation between M n,th and M n,MALS , and low dispersity ( Đ = 1.27).…”

Biomass RNA for the Controlled Synthesis of Degradable Networks by Radical Polymerization

“…Therefore, we synthesized acrylamido RNA crosslinkers under different acylation conditions (% DMSO v/v in water and the amount of AAm-AI ), and the degree of acylation was determined using 1 H NMR, according to the previously reported procedure (Figure S5). As shown in Figure B, conducting RNA modification with a higher concentration of DMSO in water or using a larger amount of AAm-AI resulted in an increased number of acrylamide incorporation in the RNA. It should be noted that up to superstoichiometric yield (12.8 acrylamide groups per 10 ribonucleotides) could be achieved when RNA was treated with 3 equiv (3×) of AAm-AI compared with ribonucleotide in 100% DMSO overnight.…”

“…Consequently, acyl imidazole chemistry has been extensively studied for the structural mapping of RNA (i.e., selective 2′-hydroxyl acylation analyzed by primer extension, SHAPE) in vitro and in vivo . We have recently demonstrated that RNA can be modified with acyl imidazole reagents to serve as an atom transfer radical polymerization (ATRP) initiator under the mild and biocompatible polymerization conditions . Additionally, it is important to note that during the radical polymerization process vinyl monomers could undergo copolymerization with two or more different types of monomers.…”

Visible-light-induced ATRP under high-pressure: synthesis of ultra-high-molecular-weight polymers

“…11–15 This advancement enables the synthesis of well-defined polymers with complex structures, like protein–polymers and nucleic acid–polymer hybrids. 16–18…”