Synthesis of Novel C4-Linked C-2-Imidazole Ribonucleoside Phosphoramidite and Its Application to Probing the Catalytic Mechanism of a Ribozyme

Lisa Araki, Keiji Morita, Maho Yamaguchi, Zheng-Yun Zhao, Timothy J. Wilson, David M. J. Lilley, Shinya Harusawa

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    The synthesis of a novel C4-linked C-2-imidazole ribonucleoside phosphoramidite (ICN-C-2-PA 1) with a two-carbon linker between imidazole and ribose moieties is described. In the phosphoramidite, POM and 2-cyanoethyl groups were selected to protect the endocyclic amine function of imidazole and the 2'-hydroxyl function of D-ribose, respectively. The C-2-imidazole nucleoside, a flexible structural mimic of a purine nucleobase, was successfully incorporated using ICN-C-2-PA 1 into position 638 of the VS ribozyme through 2'-TBDMS chemistry to study the role of G638 in general acid-base catalysis. The modified VS ribozyme (G638C(2)Imz) exhibited significantly greater catalytic activity than observed with the C-0-imidazole that has no carbon atoms linking the ribose and the C4-imidazole. Imidazole nucleoside analogues with variable spacer lengths could provide a valuable general methodology for exploring the catalytic mechanisms of ribozymes.

    Original languageEnglish
    Pages (from-to)2350-2356
    Number of pages7
    JournalJournal of Organic Chemistry
    Volume74
    Issue number6
    DOIs
    Publication statusPublished - 20 Mar 2009

    Keywords

    • DELTA VIRUS RIBOZYME
    • ACID-BASE CATALYSIS
    • GENERAL ACID
    • ACTIVE-SITE
    • HAIRPIN RIBOZYME
    • CHEMICAL-SYNTHESIS
    • RNA
    • RESCUE
    • OLIGORIBONUCLEOTIDES
    • NUCLEOSIDES

    Cite this

    @article{e51ca457a4f04f68b06a06f6ac6ac809,
    title = "Synthesis of Novel C4-Linked C-2-Imidazole Ribonucleoside Phosphoramidite and Its Application to Probing the Catalytic Mechanism of a Ribozyme",
    abstract = "The synthesis of a novel C4-linked C-2-imidazole ribonucleoside phosphoramidite (ICN-C-2-PA 1) with a two-carbon linker between imidazole and ribose moieties is described. In the phosphoramidite, POM and 2-cyanoethyl groups were selected to protect the endocyclic amine function of imidazole and the 2'-hydroxyl function of D-ribose, respectively. The C-2-imidazole nucleoside, a flexible structural mimic of a purine nucleobase, was successfully incorporated using ICN-C-2-PA 1 into position 638 of the VS ribozyme through 2'-TBDMS chemistry to study the role of G638 in general acid-base catalysis. The modified VS ribozyme (G638C(2)Imz) exhibited significantly greater catalytic activity than observed with the C-0-imidazole that has no carbon atoms linking the ribose and the C4-imidazole. Imidazole nucleoside analogues with variable spacer lengths could provide a valuable general methodology for exploring the catalytic mechanisms of ribozymes.",
    keywords = "DELTA VIRUS RIBOZYME, ACID-BASE CATALYSIS, GENERAL ACID, ACTIVE-SITE, HAIRPIN RIBOZYME, CHEMICAL-SYNTHESIS, RNA, RESCUE, OLIGORIBONUCLEOTIDES, NUCLEOSIDES",
    author = "Lisa Araki and Keiji Morita and Maho Yamaguchi and Zheng-Yun Zhao and Wilson, {Timothy J.} and Lilley, {David M. J.} and Shinya Harusawa",
    year = "2009",
    month = "3",
    day = "20",
    doi = "10.1021/jo802556s",
    language = "English",
    volume = "74",
    pages = "2350--2356",
    journal = "Journal of Organic Chemistry",
    issn = "0022-3263",
    publisher = "American Chemical Society",
    number = "6",

    }

    Synthesis of Novel C4-Linked C-2-Imidazole Ribonucleoside Phosphoramidite and Its Application to Probing the Catalytic Mechanism of a Ribozyme. / Araki, Lisa; Morita, Keiji; Yamaguchi, Maho; Zhao, Zheng-Yun; Wilson, Timothy J.; Lilley, David M. J.; Harusawa, Shinya.

    In: Journal of Organic Chemistry, Vol. 74, No. 6, 20.03.2009, p. 2350-2356.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Synthesis of Novel C4-Linked C-2-Imidazole Ribonucleoside Phosphoramidite and Its Application to Probing the Catalytic Mechanism of a Ribozyme

    AU - Araki, Lisa

    AU - Morita, Keiji

    AU - Yamaguchi, Maho

    AU - Zhao, Zheng-Yun

    AU - Wilson, Timothy J.

    AU - Lilley, David M. J.

    AU - Harusawa, Shinya

    PY - 2009/3/20

    Y1 - 2009/3/20

    N2 - The synthesis of a novel C4-linked C-2-imidazole ribonucleoside phosphoramidite (ICN-C-2-PA 1) with a two-carbon linker between imidazole and ribose moieties is described. In the phosphoramidite, POM and 2-cyanoethyl groups were selected to protect the endocyclic amine function of imidazole and the 2'-hydroxyl function of D-ribose, respectively. The C-2-imidazole nucleoside, a flexible structural mimic of a purine nucleobase, was successfully incorporated using ICN-C-2-PA 1 into position 638 of the VS ribozyme through 2'-TBDMS chemistry to study the role of G638 in general acid-base catalysis. The modified VS ribozyme (G638C(2)Imz) exhibited significantly greater catalytic activity than observed with the C-0-imidazole that has no carbon atoms linking the ribose and the C4-imidazole. Imidazole nucleoside analogues with variable spacer lengths could provide a valuable general methodology for exploring the catalytic mechanisms of ribozymes.

    AB - The synthesis of a novel C4-linked C-2-imidazole ribonucleoside phosphoramidite (ICN-C-2-PA 1) with a two-carbon linker between imidazole and ribose moieties is described. In the phosphoramidite, POM and 2-cyanoethyl groups were selected to protect the endocyclic amine function of imidazole and the 2'-hydroxyl function of D-ribose, respectively. The C-2-imidazole nucleoside, a flexible structural mimic of a purine nucleobase, was successfully incorporated using ICN-C-2-PA 1 into position 638 of the VS ribozyme through 2'-TBDMS chemistry to study the role of G638 in general acid-base catalysis. The modified VS ribozyme (G638C(2)Imz) exhibited significantly greater catalytic activity than observed with the C-0-imidazole that has no carbon atoms linking the ribose and the C4-imidazole. Imidazole nucleoside analogues with variable spacer lengths could provide a valuable general methodology for exploring the catalytic mechanisms of ribozymes.

    KW - DELTA VIRUS RIBOZYME

    KW - ACID-BASE CATALYSIS

    KW - GENERAL ACID

    KW - ACTIVE-SITE

    KW - HAIRPIN RIBOZYME

    KW - CHEMICAL-SYNTHESIS

    KW - RNA

    KW - RESCUE

    KW - OLIGORIBONUCLEOTIDES

    KW - NUCLEOSIDES

    U2 - 10.1021/jo802556s

    DO - 10.1021/jo802556s

    M3 - Article

    VL - 74

    SP - 2350

    EP - 2356

    JO - Journal of Organic Chemistry

    JF - Journal of Organic Chemistry

    SN - 0022-3263

    IS - 6

    ER -