Hiroki Kumamoto

Publications (6)11.78 Total impact

• Article: Preparation of Carbocyclic C‐Nucleosides from α‐Chlorooxime Precursor

  Ugo Pradere, Hiroki Kumamoto, Vincent Roy, Luigi A. Agrofoglio
  Annalen der Chemie und Pharmacie 12/2009; 2010(4):749 - 754. · 3.10 Impact Factor
• Article: Click Azide‐Alkyne Cycloaddition for the Synthesis of D‐(–)‐1,4‐Disubstituted Triazolo‐Carbanucleosides

  Julie Broggi, Hiroki Kumamoto, Sabine Berteina-Raboin, Steven P. Nolan, Luigi A. Agrofoglio
  Annalen der Chemie und Pharmacie 02/2009; 2009(12):1880 - 1888. · 3.10 Impact Factor
• Article: Nucleotide binding to human UMP-CMP kinase using fluorescent derivatives -- a screening based on affinity for the UMP-CMP binding site.

  Dimitri Topalis, Hiroki Kumamoto, Maria-Fernanda Amaya Velasco, Laurence Dugué, Ahmed Haouz, Julie Anne C Alexandre, Sarah Gallois-Montbrun, Pedro Maria Alzari, Sylvie Pochet, Luigi André Agrofoglio, Dominique Deville-Bonne
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  ABSTRACT: Methylanthraniloyl derivatives of ATP and CDP were used in vitro as fluorescent probes for the donor-binding and acceptor-binding sites of human UMP-CMP kinase, a nucleoside salvage pathway kinase. Like all NMP kinases, UMP-CMP kinase binds the phosphodonor, usually ATP, and the NMP at different binding sites. The reaction results from an in-line phosphotransfer from the donor to the acceptor. The probe for the donor site was displaced by the bisubstrate analogs of the Ap5X series (where X = U, dT, A, G), indicating the broad specificity of the acceptor site. Both CMP and dCMP were competitors for the acceptor site probe. To find antimetabolites for antivirus and anticancer therapies, we have developed a method of screening acyclic phosphonate analogs that is based on the affinity of the acceptor-binding site of the human UMP-CMP kinase. Several uracil vinylphosphonate derivatives had affinities for human UMP-CMP kinase similar to those of dUMP and dCMP and better than that of cidofovir, an acyclic nucleoside phosphonate with a broad spectrum of antiviral activities. The uracil derivatives were inhibitors rather than substrates of human UMP-CMP kinase. Also, the 5-halogen-substituted analogs inhibited the human TMP kinase less efficiently. The broad specificity of the enzyme acceptor-binding site is in agreement with a large substrate-binding pocket, as shown by the 2.1 A crystal structure.
  FEBS Journal 08/2007; 274(14):3704-14. · 3.79 Impact Factor
• Article: Cross-metathesis mediated synthesis of new acyclic nucleoside phosphonates.

  Vincent Roy, Hiroki Kumamoto, Sabine Berteina-Raboin, Steven P Nolan, Dimitri Topalis, Dominique Deville-Bonne, Jan Balzarini, Johan Neyts, Gracelia Andrei, Robert Snoeck, Luigi A Agrofoglio
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  ABSTRACT: With the commercial availability of well-defined ruthenium metathesis catalysts which combine high stability and broad functional group compatibility, olefin metathesis is now routinely integrated in various syntheses. We will report here the overwhelming power and scope of cross-metathesis in the area of new acyclic nucleoside phosphonates. Scope and limitations of this approach, and especially the E/Z stereocontrol, are discussed on selected examples from our drug discovery group.
  Nucleosides Nucleotides &amp Nucleic Acids 02/2007; 26(10-12):1399-402. · 0.90 Impact Factor
• Article: Looking for new pyrimidine acyclic nucleotide analogues designed for phosphorylation by human UMP-CMP kinase.

  Dimitri Topalis, Hiroki Kumamoto, Julie A C Alexandre, Laurence Dugué, Sylvie Pochet, Sabine Berteina-Raboin, Luigi A Agrofoglio, Dominique Deville-Bonne
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  ABSTRACT: Human UMP-CMP kinase is involved in the phosphorylation of nucleic acid precursors and also in the activation of antiviral analogues including cidofovir, an acyclic phosphonate compound that mimicks dCMP and shows a broad antiviral spectrum. The binding of ligands to the enzyme was here investigated using a fluorescent probe and a competitive titration assay. At the acceptor site, the enzyme was found to accommodate any base, purine and pyrimidine, including thymidine. A method for screening analogues based on their affinity for the UMP binding site was developed. The affinities of uracil vinylphosphonate derivatives modified in the 5 position were found similar to (d)UMP and (d)CMP and improved when compared to cidofovir.
  Nucleosides Nucleotides &amp Nucleic Acids 02/2007; 26(10-12):1369-73. · 0.90 Impact Factor
• Article: Preparation of acyclo nucleoside phosphonate analogues based on cross-metathesis

  Hiroki Kumamoto, Dimitri Topalis, Julie Broggi, Ugo Pradère, Vincent Roy, Sabine Berteina-Raboin, Steven P. Nolan, Dominique Deville-Bonne, Graciela Andrei, Robert Snoeck, Daniel Garin, Jean-Marc Crance, Luigi A. Agrofoglio
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  ABSTRACT: In our on-going program targeting anti-pox activity, we report here the synthesis of hitherto unknown acyclic nucleoside phosphonates using olefin cross-metathesis (CM) as a key assembly step. Modification at the C-5 position of the uracil moiety was performed under optimized Pd(0)-catalyzed Stille cross-coupling conditions. None of the obtained compounds were active against poxviruses, nor do they exhibit any toxicity.Graphical abstractIn our on-going program targeting anti-pox activity, the synthesis of various acyclic nucleoside phosphonates is described using olefin cross-metathesis reaction and Pd(0)-mediated alkylation at the C5-position of the uracil moiety.
  Tetrahedron. 64(16):3517-3526.