18684-29-2Relevant academic research and scientific papers
PHOSPHORAMIDATE DERIVATIVES OF 5 - FLUORO - 2 ' - DEOXYURIDINE FOR USE IN THE TREATMENT OF CANCER
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Page/Page column 66-67, (2012/09/21)
Phosphoramidate derivatives of 5-fluoro-2'-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.
Characterization of pyrimidine nucleoside phosphorylase of Mycoplasma hyorhinis: Implications for the clinical efficacy of nucleoside analogues
Vande Voorde, Johan,Gago, Federico,Vrancken, Kristof,Liekens, Sandra,Balzarini, Jan
experimental part, p. 113 - 123 (2012/10/23)
In the present paper we demonstrate that the cytostatic and antiviral activity of pyrimidine nucleoside analogues is markedly decreased by a Mycoplasma hyorhinis infection and show that the phosphorolytic activity of the mycoplasmas is responsible for this. Since mycoplasmas are (i) an important cause of secondary infections in immunocompromised (e.g. HIV infected) patients and (ii) known to preferentially colonize tumour tissue in cancer patients, catabolic mycoplasma enzymesmay compromise efficient chemotherapy of virus infections and cancer. In the genome of M. hyorhinis, a TP (thymidine phosphorylase) gene has been annotated. This gene was cloned, expressed in Escherichia coli and kinetically characterized. Whereas the mycoplasma TP efficiently catalyses the phosphorolysis of thymidine (Km = 473 μM) and deoxyuridine (Km = 578 μM), it prefers uridine (K m =92 μM) as a substrate. Our kinetic data and sequence analysis revealed that the annotated M. hyorhinis TP belongs to the NP (nucleoside phosphorylase)-II class PyNPs (pyrimidine NPs), and is distinct from the NP-II class TP and NPI class UPs (uridine phosphorylases). M. hyorhinis PyNP also markedly differs from TP and UP in its substrate specificity towards therapeutic nucleoside analogues and susceptibility to clinically relevant drugs. Several kinetic properties of mycoplasma PyNP were explained by in silico analyses. The Authors Journal compilation
Fluorinase-coupled base swaps: Synthesis of [18F]-5′- deoxy-5′-fluorouridines
Winkler, Margit,Domarkas, Juozas,Schweiger, Lutz F.,O'Hagan, David
supporting information; experimental part, p. 10141 - 10143 (2009/05/30)
(Chemical Equation Presented) Making F-ases: One-pot fluorination/base-swap biotransformations were developed by coupling the fluorinase enzyme to nucleoside phosphorylases to generate 5′-deoxy-5′-fluoronucleosides (FDAs). These biotransformations are amenable to radiolabeling syntheses starting from [18F]fluoride ion, as exemplified by the synthesis of [18F]-5′-deoxy-5′-fluorouridines (see scheme), and demonstrate a new application of fluorinase as a catalyst for 18F-C bond formation.
Gene therapy of cancer: activation of nucleoside prodrugs with e. colipurine nucleoside phosphorylase
Secrist III, John A.
, p. 745 - 757 (2007/10/03)
During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery of E. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. .This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data. Copyright
