Synthetic analogues of polynucleotides—I. The synthesis and properties of copolymers of 5′-o-acrylylthymidine and 5′-o-acrylyluridine with acrylamide

Cassidy, F.; Jones, A. S.

doi:10.1016/0014-3057(66)90013-9

Cited by 24 publications

(2 citation statements)

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“…One conceptual approach to this goal involves the synthesis of polymers capable of biomimetic molecular recognition of nucleic acids. Polyacrylate analogues of nucleic acids were first reported in 1966 by Jones, , followed by many other alternate backbones, including polyester, polyvinyl, and polyamide, presaging peptide nucleic acid (PNA) and other nucleic acid backbone replacement studies, although the hybridization was poorly defined and inefficient . These and other polymer nucleic acid analogues require several days of incubation with DNA to yield a hypochromic shift and exhibit a thermal transition.…”

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confidence: 99%

Synthetic Polymer Hybridization with DNA and RNA Directs Nanoparticle Loading, Silencing Delivery, and Aptamer Function

2015

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We report herein discrete triplex hybridization of DNA and RNA with polyacrylates. Length-monodisperse triazine-derivatized polymers were prepared on gram-scale by reversible addition–fragmentation chain-transfer polymerization. Despite stereoregio backbone heterogeneity, the triazine polymers bind T/U-rich DNA or RNA with nanomolar affinity upon mixing in a 1:1 ratio, as judged by thermal melts, circular dichroism, gel-shift assays, and fluorescence quenching. We call these polyacrylates “bifacial polymer nucleic acids” (bPoNAs). Nucleic acid hybridization with bPoNA enables DNA loading onto polymer nanoparticles, siRNA silencing delivery, and can further serve as an allosteric trigger of RNA aptamer function. Thus, bPoNAs can serve as tools for both non-covalent bioconjugation and structure–function nucleation. It is anticipated that bPoNAs will have utility in both bio- and nanotechnology.

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Synthetic Polymer Hybridization with DNA and RNA Directs Nanoparticle Loading, Silencing Delivery, and Aptamer Function

2015

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“…The highly heterogeneous polyacrylate backbones displaying melamine can triplex hybridize efficiently with native bases and nucleic acids and could thus help bridge native and artificial architectures, uniting nucleic acid biotechnology with new materials . Polyacrylate analogues of nucleic acids , and other backbones formed through uncontrolled polymerization have been reported, − including polyester, polyvinyl, polyamide, and others, though nucleic acid hybridization with all carbon backbones is generally inefficient. , In contrast, bifacial polymer nucleic acid (bP o NA), derived from low polydispersity polyacrylates via controlled radical polymerization (RAFT), can engage cooperatively with oligo-T/U tracts with good thermal stability and nanomolar range affinity via a biomimetic triazine, base-triple interface that forms on mixing, compatible with both polymer nanoparticle assembly as well as native RNA folding and function . It is likely that the native-like hybridization of these polyacrylates with DNA and RNA derives largely from advances in controlled radical polymerization methods such as RAFT, which produces polyacrylates with narrow polydispersity.…”

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Triplex Hybridization of siRNA with Bifacial Glycopolymer Nucleic Acid Enables Hepatocyte-Targeted Silencing

et al. 2019

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Herein, we describe a versatile non-covalent strategy for packaging nucleic acid cargo with targeting modalities, based on triplex hybridization of oligo-uridylate RNA with bifacial polymer nucleic acid (bP o NA). Polyacrylate bP o NA was prepared and side chain-functionalized with Nacetylgalactosamine (GalNAc), which is known to enable delivery to hepatocytes and liver via binding to the asialoglycoprotein receptor (ASGPR). Polymer binding resulted in successful delivery of both native and synthetically modified siRNAs to HepG2 cells in culture, yielding in low nanomolar IC 50 silencing of the endogenous ApoB target, in line with observations of expected Dicer processing of the polymer-siRNA targeting complex. Indeed, in vitro Dicer treatment of the polymer complex indicated that triplex hybridization does not impede RNA processing and release from the polymer. The complex itself elicited a quiescent immunostimulation profile relative to free RNA in a cytokine screen, setting the stage for a preliminary in vivo study in a high-calorie-diet mouse model. Gratifyingly, we observed significant ApoB silencing in a preliminary animal study, validating bP o NA as an in vivo carrier platform for systemic siRNA delivery. Thus, this new siRNA carrier platform exhibits generally useful function and is accessible through scalable synthesis. In addition to its utility as a carrier, the triplex-hybridizing synthetic platform could be useful for optimization screens of siRNA sequences using the identical polymer carriers, thus alleviating the need for covalent ligand modification of each RNA substrate.

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Polymers and copolymers containing D‐galactose residues

1969

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Polymers and copolymers based on the 6-methacrylate ester, the 6-acrylate ester, and the 6-0-ally1 ether of 1.2 : 3.4-di-O-isopropylidene-a-~-galactopyranose (diisopropylidenegalactose), and the 1-methacrylate ester of 2.3-O-isopropylideneglycerol, have been synthesised and characterised by chemical and infrared analysis. Methods have been developed for removing the protecting isopropylidene groups from the polymerised products to reveal the hydrophilic, hydroxylated carbohydrate residues.By comparing the properties (e.g. glass transition temperature, hydrolysis of isopropylidene residues, and crosslinking reactions) of galactose methacrylate and glycerol methacrylate polymers, it is possible to assess the influence of the heterocyclic ring and glycosidic hydroxyl group of the galactose moiety in synthetic polymer systems.A series of galactose methacrylate-methyl methacrylate random copolymers, containing different proportions of sugar residues, has been prepared, and it has been shown that the hydrophilic properties can be accurately controlled by the amount of galactose methacrylate in the copolymer. The industrial significance of this is discussed.Successful copolymerisations of diisopropylidenegalactose acrylate and methyl acrylate, diisopropylidenegalactose methacrylate and styrene, diisopropylidenegalactose acrylate and acrylonitrile, diisopropylidenegalactose methacrylate and vinyl acetate, and ally1 diisopropylidenegalactose and maleic anhydride are described, and in most cases the COpolymers have been readily deacetonated and characterised by phenylhydrazone formation.Evidence is presented to show that, in general, the introduction of reducing sugar units is a convenient method of increasing the reactivity and hydrophilicity of synthetic polymers and copolymers. ZUSAMMENFASSUNG:Polymere und Copolymere aus dem 6-Methacrylsaureester, dem 6-Acrylsaureester und dem 6-0-Allylather der 1.2 : 3.4-Di-O-isopropyliden-a-~-galaktopyranose (Diisopropylidengalaktose) sowie dem 1-Methacrylsaureester des 2.3-0-Isopropylidenglycerins wurden synthetisiert und durch chemische und IR-Analyse charakterisiert. Methoden mr Entfernung der Isopropyliden-Schutzgruppen aus den polymeren Produkten wurden entwickelt, u m die hydrophilen, hydroxylhaltigen Kohlenhydratreste freizusetzen.Durch Vergleich der Eigenschaften der Galaktosemethacrylat-und Glycerinmethacrylat-Polymeren (2. B. Glasumwandlungstemperatur, Hydrolyse der Isopropylidenreste, Vernetzungsreaktionen) ist es moglich, den EinfluR des heterocyclischen Ringes und der glykosidischen Hydroxylgruppe des Galaktoserestes in synthetischen Polymeren abzuschatzen. Polymers and Copolymers Containing D-Galactose ResiduesEine Reihe von statistischen Galaktosemethacrylat-Methylmethacrylat-Copolymeren mit verschiedenem Gehalt an Zuckerresten wurden hergestellt, deren hydrophile Eigenschaften durch den Gehalt an Galaktosemethacrylat genau kontrolliert werden konnen. Ihre industrielle Bedeutung wird diskutiert.Es werden erfolgreiche Copolymer isationen von Diisopropylidengalaktose-meth...

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Synthetic analogues of polynucleotides—I. The synthesis and properties of copolymers of 5′-o-acrylylthymidine and 5′-o-acrylyluridine with acrylamide

Cited by 24 publications

References 3 publications

Synthetic Polymer Hybridization with DNA and RNA Directs Nanoparticle Loading, Silencing Delivery, and Aptamer Function

Synthetic Polymer Hybridization with DNA and RNA Directs Nanoparticle Loading, Silencing Delivery, and Aptamer Function

Triplex Hybridization of siRNA with Bifacial Glycopolymer Nucleic Acid Enables Hepatocyte-Targeted Silencing

Polymers and copolymers containing D‐galactose residues

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