Facile solid-phase synthesis of a highly stable poly(ethylene glycol)–oligonucleotide conjugate

Ikeda, Yutaka; Kawasaki, Hiromichi; Ichinohe, Satoshi; Nagasaki, Yukio

doi:10.1039/c2tb00031h

Cited by 3 publications

(8 citation statements)

References 16 publications

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“…In this regard, PEGylation has been shown to be one of the most effective and widely used strategies. 38 , 39 PEGylation can provide a flexible, hydrophilic shield to minimize the nonspecific uptake and removal by macrophages. Indeed, PEGylation has shown to be effective at resisting nonspecific adsorption of biomolecules on both flat and curved nanoparticle (e.g., magnetic nanoparticle, quantum dot) surfaces.…”

Section: Resultsmentioning

confidence: 99%

Terminal PEGylated DNA–Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents

Song

Guo

Roebuck

et al. 2015

ACS Appl. Mater. Interfaces

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Over the past 10 years, polyvalent DNA–gold nanoparticle (DNA–GNP) conjugate has been demonstrated as an efficient, universal nanocarrier for drug and gene delivery with high uptake by over 50 different types of primary and cancer cell lines. A barrier limiting its in vivo effectiveness is limited resistance to nuclease degradation and nonspecific interaction with blood serum contents. Herein we show that terminal PEGylation of the complementary DNA strand hybridized to a polyvalent DNA–GNP conjugate can eliminate nonspecific adsorption of serum proteins and greatly increases its resistance against DNase I-based degradation. The PEGylated DNA–GNP conjugate still retains a high cell uptake property, making it an attractive intracellular delivery nanocarrier for DNA binding reagents. We show that it can be used for successful intracellular delivery of doxorubicin, a widely used clinical cancer chemotherapeutic drug. Moreover, it can be used for efficient delivery of some cell-membrane-impermeable reagents such as propidium iodide (a DNA intercalating fluorescent dye currently limited to the use of staining dead cells only) and a diruthenium complex (a DNA groove binder), for successful staining of live cells.

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Section: Resultsmentioning

confidence: 99%

Terminal PEGylated DNA–Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents

Song

Guo

Roebuck

et al. 2015

ACS Appl. Mater. Interfaces

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“…The synthesis procedure is summarized in Scheme . Compound 1 , which was synthesized as previously reported, was used as an initiator for the polymerization of ethylene oxide to afford the PEG derivative 2 ( M n : 9.50 × 10 3 and MWD: 1.19 determined by SEC diagram) The hydroxyl end of the PEG molecule was capped with CH 3 I (Figure S2) to protect PEG chain from undesired oxidation reactions. The osmium oxidation of compound 3 ( M n : 1.00 × 10 4 and MWD: 1.13 determined by SEC diagram) afforded the diol compound 4 ( M n : 9.32 × 10 3 and MWD: 1.14 determined by SEC diagram); subsequent oxidation by sodium periodate afforded compound 5 .…”

Section: Resultsmentioning

confidence: 99%

“…Tetrahydrofuran (THF), benzene (reagent-grade; Kanto Chemical Co., Inc., Tokyo, Japan), and ethylene oxide (EO; 100%; Sumitomo Seika Chemicals Co., Ltd., Hyogo, Japan) were purified conventionally. A THF solution of potassium naphthalene was prepared by a method described in the previous paper . PEG (5 kDa) possessing an activated ester (PEG-NHS) was purchased from NOF.…”

Section: Methodsmentioning

confidence: 99%

Novel Protein PEGylation Chemistry via Glutalaldehyde-Functionalized PEG

Ikeda

Katamachi²,

Kawasaki³

et al. 2013

Bioconjugate Chem.

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Several PEGylated proteins have been approved as therapeutic drugs. In many cases, PEGylated protein has been synthesized by the conjugation reaction between PEG possessing activated ester and amine(s) in the protein. This reaction, however, often causes inactivation of PEGylated proteins. In this report, we present a novel chemistry which enables the PEGylation of proteins under the mild reaction condition. PEGylated lysozyme prepared by the method developed increased the biological activity of the PEGylated lysozyme more than 20 times compared with the PEGylated lysozyme prepared by the conventional method.

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“…In most cases, a low‐molecular‐weight PEG (i.e., <1000 Da) has been used for oligonucleotide modification; however, high‐molecular‐weight PEG is crucial to improving the stability of the conjugate, as stated above. Recently, our group developed a new solid phase method that enables solid‐phase synthesis of a PEG‐oligonucleotide conjugate (Figure 1) . A prepared solid phase method was preinstalled with linear PEG (5 kDa) to provide oligonucleotides modified with PEG at the 3′ terminus.…”

Section: Pegylation Of Nucleic Acidmentioning

confidence: 99%

“…Time course of the degradation of the DNA‐PEG (a) and RNA‐PEG (b). Closed circle: PEG‐oligonucleotide conjugate modified at the 3′ terminus by newly developed method, Closed triangle: PEG‐oligonucleotide conjugate modified at the 5′ terminus by conventional method . Reproduced from Ref , with permission from The Royal Society of Chemistry.…”

Section: Pegylation Of Nucleic Acidmentioning

confidence: 99%

Impacts of PEGylation on the gene and oligonucleotide delivery system

Ikeda

Nagasaki

2013

J of Applied Polymer Sci

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Poly(ethylene glycol) (PEG) is the most widely used polymer and also the gold standard in the field of drug delivery. Therapeutic oligonucleotides, for example, are modified with PEG at the terminus to increases nuclease resistance and the circulating half-lives. The surface of nanoparticle such as micelle and liposome has been also modified with PEG. At present, one PEGylated therapeutic oligonucleotide has been approved for the market and several more PEGylated products including oligonucleotide and liposome are being tested in clinical settings. This review summarizes the methods and effects of PEGylation on gene delivery. V C 2013Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40293.

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Facile solid-phase synthesis of a highly stable poly(ethylene glycol)–oligonucleotide conjugate

Cited by 3 publications

References 16 publications

Terminal PEGylated DNA–Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents

Terminal PEGylated DNA–Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents

Novel Protein PEGylation Chemistry via Glutalaldehyde-Functionalized PEG

Impacts of PEGylation on the gene and oligonucleotide delivery system

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