研究者詳細 - 木村　康明

論文 - 木村　康明

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Internal cap-initiated translation for efficient protein production from circular mRNA.

Fukuchi K, Nakashima Y, Abe N, Kimura S, Hashiya F, Shichino Y, Liu Y, Ogisu R, Sugiyama S, Kawaguchi D, Inagaki M, Meng Z, Kajihara S, Tada M, Uchida S, Li TT, Maity R, Kawasaki T, Kimura Y, Iwasaki S, Abe H

Nature biotechnology 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Biotechnology

Circular mRNA faces challenges in enhancing its translation potential as an RNA therapeutic. Here we introduce two molecular designs that bolster circular mRNA translation through an internal cap-initiated mechanism. The first consists of a circular mRNA with a covalently attached N7-methylguanosine (m7G) cap through a branching structure (cap-circ mRNA). This modification allows circular mRNA to recruit translation machinery and produce proteins more efficiently than internal ribosome entry site (IRES)-containing circular mRNAs. Combining with an N1-methylpseudouridine (m1Ψ) modification, cap-circ mRNA exhibits a lower acute immunostimulatory effect, maintaining high translation in mice. The second design features the non-covalent attachment of an m7G cap to a circular mRNA through hybridization with an m7G cap-containing oligonucleotide, enhancing translation by more than 50-fold. This setup allows circular mRNAs to synthesize reporter proteins upon hybridizing with capped mRNAs or long non-coding RNAs and to undergo rolling circle-type translation. These advancements broaden the therapeutic applications of circular mRNAs by minimizing their molecular size, elevating translation efficiency and facilitating cell-type-selective translation.

DOI： 10.1038/s41587-025-02561-8

Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures 査読有り

Inagaki, M; Abe, N; Li, ZM; Nakashima, Y; Acharyya, S; Ogawa, K; Kawaguchi, D; Hiraoka, H; Banno, A; Meng, ZY; Tada, M; Ishida, T; Lyu, P; Kokubo, K; Murase, H; Hashiya, F; Kimura, Y; Uchida, S; Abe, H

NATURE COMMUNICATIONS 14 巻 ( 1 ) 頁： 2657 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Communications

Starting with the clinical application of two vaccines in 2020, mRNA therapeutics are currently being investigated for a variety of applications. Removing immunogenic uncapped mRNA from transcribed mRNA is critical in mRNA research and clinical applications. Commonly used capping methods provide maximum capping efficiency of around 80–90% for widely used Cap-0- and Cap-1-type mRNAs. However, uncapped and capped mRNA possesses almost identical physicochemical properties, posing challenges to their physical separation. In this work, we develop hydrophobic photocaged tag-modified cap analogs, which separate capped mRNA from uncapped mRNA by reversed-phase high-performance liquid chromatography. Subsequent photo-irradiation recovers footprint-free native capped mRNA. This approach provides 100% capping efficiency even in Cap-2-type mRNA with versatility applicable to 650 nt and 4,247 nt mRNA. We find that the Cap-2-type mRNA shows up to 3- to 4-fold higher translation activity in cultured cells and animals than the Cap-1-type mRNA prepared by the standard capping method.

DOI： 10.1038/s41467-023-38244-8

mRNAの完全化学合成を可能とする化学的キャップ化法の開発

阿部洋, 小川和哉, 阿部奈保子, 木村康明

MEDCHEM NEWS 33 巻 ( 2 ) 頁： 75 - 78 2023年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：公益社団法人日本薬学会

近年、新型コロナウイルス感染症においてmRNAワクチンが大きな成功を収めた。しかし、mRNAワクチンは、mRNAの生体内不安定性等による活性の低下が課題としてあげられる。そこで、安定性向上が見込まれる化学修飾をmRNAに導入することが効果的であるが、それを実現するための汎用的合成法は存在しない。本研究ではmRNAへの化学修飾の導入の障壁となる酵素法を回避したmRNAの完全化学合成法を開発した。本手法では、mRNAに対して位置特異的な化学修飾の導入が可能であり、適切な化学修飾パターンにより翻訳活性と安定性の最大化が可能となる。本稿では、完全化学合成法の開発経緯、完全化学合成法による化学修飾mRNAの構造活性相関および本手法で合成したmRNAがんワクチンの治療効果について解説する。

DOI： 10.14894/medchem.33.2_75

SYNTHESIS AND BIOLOGICAL EVALUATION OF NMDI14 DERIVATIVES AS ANTI-MESOTHELIOMA AGENTS 国際誌

Hong Nhung Nguyen, Suzuki Koya, Kimura Yasuaki, Hirokawa Takatsugu, Murakami-Tonami Yuko, Abe Hiroshi

HETEROCYCLES 100 巻 ( 2 ) 頁： 253 - 266 2020年2月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Heterocycles

Mesothelioma is a severe tumor formed in pleura and peritoneum, for which no useful molecular-targeting therapy is available. We synthesized several derivatives of NMDI14, which is a reported inhibitor for non-sense mediated mRNA decay, and evaluated the activity of the NMDI14 derivatives as potential anti-mesothelioma agents. Some of the synthesized compounds showed promising activity in terms of cytotoxicity toward mesothelioma model cells and promotion of GAS5 expression selectively in mesothelioma cells. These results indicate that the NMDI14 derivatives may be useful for further developing clinically effective anti-mesothelioma drugs.

DOI： 10.3987/COM-19-14191

Intracellular Delivery of Antisense DNA and siRNA with Amino Groups Masked with Disulfide Units 国際誌

Shu Zhaoma, Ota Azumi, Takayama Yukiya, Katsurada Yuri, Kusamori Kosuke, Abe Naoko, Nakamoto Kosuke, Tomoike Fumiaki, Tada Seiichi, Ito Yoshihiro, Nishikawa Makiya, Kimura Yasuaki, Abe Hiroshi

CHEMICAL & PHARMACEUTICAL BULLETIN 68 巻 ( 2 ) 頁： 129 - 132 2020年2月

Intracellular Delivery of Antisense DNA and siRNA with Amino Groups Masked with Disulfide Units. 国際誌

Shu Z, Ota A, Takayama Y, Katsurada Y, Kusamori K, Abe N, Nakamoto K, Tomoike F, Tada S, Ito Y, Nishikawa M, Kimura Y, Abe H

Chemical & pharmaceutical bulletin 68 巻 ( 2 ) 頁： 129 - 132 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Chemical & pharmaceutical bulletin

Efficient methods for delivery of antisense DNA or small interfering RNA (siRNA) are highly needed. Cationic materials, which are conventionally used for anionic oligonucleotide delivery, have several drawbacks, including aggregate formation, cytotoxicity and a low endosome escape efficiency. In this report a bio-reactive mask (i.e., disulfide unit) for cationic amino groups was introduced, and the mask was designed such that it was removed at the target cell surface. Insolubility and severe cellular toxicity caused by exposed cationic groups are avoided when using the mask. Moreover, the disulfide unit used to mask the cationic group enabled direct delivery of oligonucleotides to the cell cytosol. The molecular design reported is a promising approach for therapeutic applications.

DOI： 10.1248/cpb.c19-00811

Disulfide-Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA. 国際誌

Shu Z, Tanaka I, Ota A, Fushihara D, Abe N, Kawaguchi S, Nakamoto K, Tomoike F, Tada S, Ito Y, Kimura Y, Abe H

Angewandte Chemie (International ed. in English) 58 巻 ( 20 ) 頁： 6611 - 6615 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Angewandte Chemie - International Edition

Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported methods using liposomes or receptor-ligands take several hours or more to deliver oligonucleotides to the cytoplasm due to their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach the cytoplasm 10 minutes after administration to cultured cells. This rapid cytoplasmic internalization of disulfide-modified oligonucleotides suggests the existence of an uptake pathway other than endocytosis. Mechanistic analysis revealed that the modified oligonucleotides are efficiently internalized into the cytoplasm through disulfide exchange reactions with the thiol groups on the cellular surface. This approach solves several critical problems with the currently available methods for enhancing cellular uptake of oligonucleotides and may be an effective approach in the medicinal application of antisense DNA and siRNA.

DOI： 10.1002/anie.201900993

Nano structure design for RNA interference

Shu, Z; Abe, N; Tomoike, F; Kimura, Y; Ito, Y; Abe, H

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 255 巻頁： . 2018年3月

Concise Affinity-Based Purification of Ligated mRNA for Structure-Activity Relationship Studies of Nucleosugar Modification Patterns. 査読有り国際誌

Yamada H, Iwai H, Hashiya F, Kimura Y, Abe H, Yamamoto J

Chembiochem : a European journal of chemical biology 26 巻 ( 2 ) 頁： e202400711 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ChemBioChem

Position-specific nucleoside sugar modifications have been shown to improve the translational activity and stability of chemically synthesized mRNA. For pharmaceutical applications of chemically modified mRNAs, a rapid purification methodology is imperative to identify the optimal modification pattern. However, while the chemical synthesis of mRNAs can be accomplished by splint ligation of oligonucleotide fragments, the current purification method for ligated mRNAs based on denaturing polyacrylamide gel electrophoresis tends to be time consuming. In this study, we developed a two-step affinity purification method for rapid sample preparation. In this method, ligated mRNA is captured by oligo dT magnetic beads and streptavidin magnetic beads with 3’-biotinylated oligo DNA, which are complementary to the 3’-poly(A) and 5’ terminal sequences of the target mRNA, respectively. Therefore, the target mRNA can be isolated from a complex mixture of splint ligations. Using this method, six sugar-modified mRNAs were simultaneously purified, and the translational activities of these mRNAs were evaluated immediately after purification. The results demonstrate that this methodology is suitable for the rapid preparation of various chemically synthesized mRNAs to identify their optimal modification patterns.

DOI： 10.1002/cbic.202400711

Position-Specific Nucleoside Sugar Modifications in mRNA ORF: Enhancing Translational Function through Complete Chemical Synthesis of mRNA

Hiroshi Abe, Yasuaki Kimura, Masakazu Honma, Kosuke Nakamoto, Keiichi Motosawa, Takayuki Atago, Kana Asano, Fumitaka Hashiya, Naoko Abe, Keiko Kobayashi, Ryoko Ogisu, Atsushi Hashimoto, Keiko Hiraishi, Seiji Saito, Junichiro Yamamoto, Hiroto Iwai

2024年12月

Development of hydrophobic tag purifying monophosphorylated RNA for chemical synthesis of capped mRNA and enzymatic synthesis of circular mRNA. 査読有り国際誌 Open Access

Ototake M, Inagaki M, Kimura S, Onda K, Tada M, Kawaguchi D, Murase H, Fukuchi K, Gao Y, Kokubo K, Acharyya S, Meng Z, Ishida T, Kawasaki T, Abe N, Hashiya F, Kimura Y, Abe H

Nucleic acids research 52 巻 ( 20 ) 頁： 12141 - 12157 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nucleic Acids Research

We developed phosphorylation reagents with a nitrobenzyl hydrophobic tag and used them for 5′-phosphorylation of chemically or transcriptionally synthesized RNA. The capability of hydrophobic tags to synthesize 5′-monophosphorylated RNA was evaluated based on the yield of the desired oligonucleotides, stability of protecting groups during cleavage/deprotection, separation ability in reverse-phase HPLC (RP-HPLC), and deprotection efficiency after RP-HPLC purification. The results showed that a nitrobenzyl derivative with a tert-butyl group at the benzyl position was most suitable for RNA 5′-phosphorylation. Using the developed phosphorylation reagent, we chemically synthesized 5′-phosphorylated RNA and confirmed that it could be purified by RP-HPLC and the following deprotection. In addition, we demonstrated complete chemical synthesis of minimal mRNA by chemical capping of 5′-monophosphorylated RNA. Ribonucleoside 5′-monophosphates with hydrophobic protecting groups have also been developed and used as substrates to transcriptionally synthesize 5′-phosphorylated RNA with >1000 bases. From the mixture of the by-products and the desired RNA, only 5′-monophosphorylated RNA could be effectively isolated by RP-HPLC. Furthermore, monophosphorylated RNA can be converted into circular mRNA via RNA ligase-mediated cyclization. Circular mRNA expression of nanoluciferase in cultured cells and mice. These techniques are important for the production of chemically synthesized mRNA and circular mRNA.

DOI： 10.1093/nar/gkae847

Internal cap-initiated translation provides efficient protein production from circular mRNA

hiroshi abe, Kosuke Fukuchi, Yuko Nakashima, Naoko Abe, Seigo Kimura, Fumitaka Hashiya, Yuichi Shichino, Satomi Sugiyama, Daisuke Kawaguchi, Masahito Inagaki, Zheyu Meng, Shiryu Kajihara, Mizuki Tada, Satoshi Uchida, Ting-Ting Li, Yiwei Liu, Ramkrishna Maity, Yasuaki Kimura, Shintaro Iwasaki, Ryoko Ogisu, Tairin Kawasaki

2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

<title>Abstract</title>
<p>Circular mRNA, emerging as a groundbreaking RNA therapeutic strategy, faces challenges in enhancing its translation potential. Here, we introduce two innovative molecular designs that bolster circular mRNA translation through an internal cap-initiated mechanism. The first design involved a circular mRNA with a covalently attached <italic>N</italic><sup>7</sup>-methylguanosine (m<sup>7</sup>G) cap through a branching structure (cap-circ mRNA). This modification allows circular mRNA to recruit translation machinery and produce proteins more efficiently than IRES-containing circular mRNAs. Combining <italic>N</italic><sup>1</sup>-methylpseudouridine (m<sup>1</sup>Ψ) modification, cap-circ mRNA exhibits a lower acute immunostimulatory effect, maintaining high translation ability, in mice. The second design features the non-covalent attachment of an m<sup>7</sup>G cap to a circular mRNA through hybridization with an m<sup>7</sup>G cap-containing oligonucleotide, significantly enhancing translation by more than 50-fold. This setup allows the design of circular mRNAs to synthesize reporter proteins upon hybridizing with capped mRNAs or long non-coding RNAs and to undergo rolling circle-type translation. These advancements have broadened the therapeutic applications of circular mRNA by minimizing their molecular size, elevating translation efficiency, and facilitating cell-type selective translation.</p>

DOI： 10.21203/rs.3.rs-4203658/v1

Intracellular Delivery of Antisense Oligonucleotides by Tri-Branched Cyclic Disulfide Units. 査読有り国際誌 Open Access

Lyu F, Hakariya H, Hiraoka H, Li Z, Matsubara N, Soo Y, Hashiya F, Abe N, Shu Z, Nakamoto K, Kimura Y, Abe H

ChemMedChem 19 巻 ( 20 ) 頁： e202400472 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ChemMedChem

Therapeutic oligonucleotides, such as antisense DNA, show promise in treating previously untreatable diseases. However, their applications are still hindered by the poor membrane permeability of naked oligonucleotides. Therefore, it is necessary to develop efficient methods for intracellular oligonucleotide delivery. Previously, our group successfully developed disulfide-based Membrane Permeable Oligonucleotides (MPON), which achieved enhanced cellular uptake and gene silencing effects through an endocytosis-free uptake mechanism. Herein, we report a new molecular design for the next generation of MPON, called trimer MPON. The trimer MPON consists of a tri-branched backbone, three α-lipoic acid units, and a spacer linker between the oligonucleotides and tri-branched cyclic disulfide unit. We describe the design, synthesis, and functional evaluation of the trimer MPON, offering new insights into the molecular design for efficient oligonucleotide delivery.

DOI： 10.1002/cmdc.202400472

Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs. 査読有り Open Access

Nomura K, An S, Kobayashi Y, Kondo J, Shi T, Murase H, Nakamoto K, Kimura Y, Abe N, Ui-Tei K, Abe H

Nucleic acids research 52 巻 ( 18 ) 頁： 10754 - 10774 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nucleic Acids Research

In this study, we report the synthesis of 2′-formamidonucleoside phosphoramidite derivatives and their incorporation into siRNA strands to reduce seed-based off-target effects of small interfering RNAs (siRNAs). Formamido derivatives of all four nucleosides (A, G, C and U) were synthesized in 5-11 steps from commercial compounds. Introducing these derivatives into double-stranded RNA slightly reduced its thermodynamic stability, but X-ray crystallography and CD spectrum analysis confirmed that the RNA maintained its natural A-form structure. Although the introduction of the 2′-formamidonucleoside derivative at the 2nd position in the guide strand of the siRNA led to a slight decrease in the on-target RNAi activity, the siRNAs with different sequences incorporating 2′-formamidonucleoside with four kinds of nucleobases into any position other than 2nd position in the seed region revealed a significant suppression of off-target activity while maintaining on-target RNAi activity. This indicates that 2′-formamidonucleosides represent a promising approach for mitigating off-target effects in siRNA therapeutics.

DOI： 10.1093/nar/gkae741

2'-β-Methylselenyl nucleos(t)ide analogs as reverse transcriptase inhibitors against diverse HIV mutants. 査読有り Open Access

Yoshida Y, Niimi Y, Fushihara D, Katakura H, Fukui R, Murase H, Tomoike F, Hashiya F, Murakami T, Kodama EN, Suzuki T, Yasukawa K, Kimura Y, Abe H

Bioorganic & medicinal chemistry 110 巻頁： 117813 - 117813 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Bioorganic and Medicinal Chemistry

Nucleoside reverse transcriptase inhibitors (NRTIs) have been extensively studied as drugs targeting HIV RT. However, the practice or use of approved NRTIs lacking the 3ʹ-hydroxy group often promotes frequent HIV mutations and generates drug-resistance. Here, we describe a novel NRTI with 2′-β-methylselenyl modification. We found that this modification inhibited the DNA elongation reaction by HIV-1 RT despite having a 3′-hydroxy group. Moreover, the conformation of this nucleoside analog is controlled at C3′-endo, a conformation that resists excision from the elongating DNA by HIV RT. Accordingly, the designed analogs exhibited activity against both wild-type HIV and multidrug-resistant HIV mutants.

DOI： 10.1016/j.bmc.2024.117813

Development of PCR primers enabling the design of flexible sticky ends for efficient concatenation of long DNA fragments. 査読有り Open Access

Nomura K, Onda K, Murase H, Hashiya F, Ono Y, Terai G, Oka N, Asai K, Suzuki D, Takahashi N, Hiraoka H, Inagaki M, Kimura Y, Shimizu Y, Abe N, Abe H

RSC chemical biology 5 巻 ( 4 ) 頁： 360 - 371 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：RSC Chemical Biology

We developed chemically modified PCR primers that allow the design of flexible sticky ends by introducing a photo-cleavable group at the phosphate moiety. Nucleic acid derivatives containing o-nitrobenzyl photo-cleavable groups with a tert-butyl group at the benzyl position were stable during strong base treatment for oligonucleotide synthesis and thermal cycling in PCR reactions. PCR using primers incorporating these nucleic acid derivatives confirmed that chain extension reactions completely stopped at position 1 before and after the site of the photo-cleavable group was introduced. DNA fragments of 2 and 3 kbp, with sticky ends of 50 bases, were successfully concatenated with a high yield of 77%. A plasmid was constructed using this method. Finally, we applied this approach to construct a 48.5 kbp lambda phage DNA, which is difficult to achieve using restriction enzyme-based methods. After 7 days, we were able to confirm the generation of DNA of the desired length. Although the efficiency is yet to be improved, the chemically modified PCR primer offers potential to complement enzymatic methods and serve as a DNA concatenation technique.

DOI： 10.1039/d3cb00212h

Development and Comparison of 4-Thiouridine to Cytidine Base Conversion Reaction. 査読有り Open Access

Ohashi S, Nakamura M, Acharyya S, Inagaki M, Abe N, Kimura Y, Hashiya F, Abe H

ACS omega 9 巻 ( 8 ) 頁： 9300 - 9308 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACS Omega

To study transcriptome dynamics without harming cells, it is essential to convert chemical bases. 4-Thiouridine (4sU) is a biocompatible uridine analogue that can be converted into a cytidine analogue. Although several reactions can convert 4sU into a cytidine analogue, few studies have compared the features of these reactions. In this study, we performed three reported base conversion reactions, including osmium tetroxide, iodoacetamide, and sodium periodate treatment, as well as a new reaction using 2,4-dinitrofluorobenzene. We compared the reaction time, conversion efficacy, and effects on reverse transcription. These reactions successfully converted 4sU into a cytidine analogue quantitatively using trinucleotides. However, the conversion efficacy and effect on reverse transcription vary depending on the reaction with the RNA transcript. OsO4 treatment followed by NH4Cl treatment showed the best base-conversion efficiency. Nevertheless, each reaction has its own advantages and disadvantages as a tool for studying the transcriptome. Therefore, it is crucial to select the appropriate reaction for the target of interest.

DOI： 10.1021/acsomega.3c08516

Topological capture of mRNA for silencing gene expression. 査読有り

Lyu F, Tomita T, Abe N, Hiraoka H, Hashiya F, Nakashima Y, Kajihara S, Tomoike F, Shu Z, Onizuka K, Kimura Y, Abe H

Chemical communications (Cambridge, England) 59 巻 ( 77 ) 頁： 11564 - 11567 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Chemical Communications

We describe herein topological mRNA capture using branched oligodeoxynucleotides (ODNs) with multiple reactive functional groups. These fragmented ODNs efficiently formed topological complexes on template mRNA in vitro. In cell-based experiments targeting AcGFP mRNA, the bifurcated reactive ODNs showed a much larger gene silencing effect than the corresponding natural antisense ODN.

DOI： 10.1039/d2cc06189a

The Effect of γ Phosphate Modified Deoxynucleotide Substrates on PCR Activity and Fidelity. 査読有り国際誌 Open Access

Hashiya F, Murase H, Chandela A, Hiraoka H, Inagaki M, Nakashima Y, Abe N, Nakamura M, Terai G, Kimura Y, Ando K, Oka N, Asai K, Abe H

Chembiochem : a European journal of chemical biology 24 巻 ( 14 ) 頁： e202200572 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ChemBioChem

Controlling PCR fidelity is an important issue for molecular biology and high-fidelity PCR is essential for gene cloning. In general, fidelity control is achieved by protein engineering of polymerases. In contrast, only a few studies have reported controlling fidelity using chemically modified nucleotide substrates. In this report, we synthesized nucleotide substrates possessing a modification on Pγ and evaluated the effect of this modification on PCR fidelity. One of the substrates, nucleotide tetraphosphate, caused a modest decrease in Taq DNA polymerase activity and the effect on PCR fidelity was dependent on the type of mutation. The use of deoxyadenosine tetraphosphate enhanced the A : T→G : C mutation dramatically, which is common when using Taq polymerase. Conversely, deoxyguanosine tetraphosphate (dG4P) suppressed this mutation but increased the G : C→A : T mutation during PCR. Using an excess amount of dG4P suppressed both mutations successfully and total fidelity was improved.

DOI： 10.1002/cbic.202200572

Synthesis of nucleoside oligophosphates by electrophilic activation of phosphorothioate. 査読有り

Hasegawa S, Inagaki M, Kato S, Li Z, Kimura Y, Abe H

Organic & biomolecular chemistry 21 巻 ( 19 ) 頁： 3997 - 4001 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Organic and Biomolecular Chemistry

We herein report a new synthetic method for nucleoside oligophosphates based on electrophilic activation of 5′-phosphorothioate nucleotides. The treatment of phosphorothioate with 2,4-dinitrochlorobenzene (DNCB) efficiently afforded the key activated species, electrophilic thioester nucleotides (EPT-Ns), which were coupled with various phosphate reagents to afford the target nucleoside oligophosphates, including an mRNA cap analog.

DOI： 10.1039/d2ob02260e

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