1904-98-9Relevant articles and documents
Thermodynamic Reaction Control of Nucleoside Phosphorolysis
Kaspar, Felix,Giessmann, Robert T.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
supporting information, p. 867 - 876 (2020/01/24)
Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).
Continuous fluorescence assays for reactions involving adenine
Firestone, Ross,Cameron, Scott,Tyler, Peter,Ducati, Rodrigo,Spitz, Adam,Schramm, Vern
, p. 11860 - 11867 (2018/04/25)
5′-Methylthioadenosine phosphorylase (MTAP) and 5′-methylthioadenosine nucleosidase (MTAN) catalyze the phosphorolysis and hydrolysis of 5′-methylthioadenosine (MTA), respectively. Both enzymes have low KM values for their substrates. Kinetic assays for these enzymes are challenging, as the ultraviolet absorbance spectra for reactant MTA and product adenine are similar. We report a new assay using 2-amino-5′-methylthioadenosine (2AMTA) as an alternative substrate for MTAP and MTAN enzymes. Hydrolysis or phosphorolysis of 2AMTA forms 2,6-diaminopurine, a fluorescent and easily quantitated product. We kinetically characterize 2AMTA with human MTAP, bacterial MTANs and use 2,6-diaminopurine as a fluorescent substrate for yeast adenine phosphoribosyltransferase. 2AMTA was used as the substrate to kinetically characterize the dissociation constants for three-transition-state analogue inhibitors of MTAP and MTAN. Kinetic values obtained from continuous fluorescent assays with MTA were in good agreement with previously measured literature values, but gave smaller experimental errors. Chemical synthesis from ribose and 2,6-dichloropurine provided crystalline 2AMTA as the oxalate salt. Chemo-enzymatic synthesis from ribose and 2,6-diaminopurine produced 2-amino-S-adenosylmethionine for hydrolytic conversion to 2AMTA. Interaction of 2AMTA with human MTAP was also characterized by pre-steady-state kinetics and by analysis of the crystal structure in a complex with sulfate as a catalytically inert analogue of phosphate. This assay is suitable for inhibitor screening by detection of fluorescent product, for quantitative analysis of hits by rapid and accurate measurement of inhibition constants in continuous assays, and pre-steady-state kinetic analysis of the target enzymes.
Nanoporous metal oxides with tunable and nanocrystalline frameworks via conversion of metal-organic frameworks
Kim, Tae Kyung,Lee, Kyung Joo,Cheon, Jae Yeong,Lee, Jae Hwa,Joo, Sang Hoon,Moon, Hoi Ri
supporting information, p. 8940 - 8946 (2013/07/26)
Nanoporous metal oxide materials are ubiquitous in the material sciences because of their numerous potential applications in various areas, including adsorption, catalysis, energy conversion and storage, optoelectronics, and drug delivery. While synthetic
PEPTIDE NUCLEIC ACID DERIVATIVES WITH GOOD CELL PENETRATION AND STRONG AFFINITY FOR NUCLEIC ACID
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, (2011/08/04)
The present invention provides a novel class of peptide nucleic acid derivatives, which show good cell penetration and strong binding affinity for nucleic acid.
PURINE NUCLEOSIDE ANALOGS
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Page/Page column 26-27, (2008/06/13)
The present invention is directed to purine nucleoside analogs of the general Formula (I), or tautomers thereof, physiologically acceptable salts, solvents and physiologically functional derivatives thereof, and pharmaceutical compositions comprising such compounds, salts and derivatives, which are useful as anti-bacterial and anti-protozoan agents. The invention is also directed to methods for treating a bacterial or protozoan infection in a mammal and use of the compounds for inhibiting the growth of a bacteria or protozoa.
Composition of matter having bioactive properties
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, (2008/06/13)
Particles of coordinated complex comprising a basic, hydrous polymer and a capacitance adding compound, as well as methods for their production, are described. These complexes exhibit a high degree of bioactivity making them suitable for a broad range of applications through their incorporation into conventional vehicles benefiting from antimicrobial and similar properties.
9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives
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, (2008/06/13)
The present invention relates to 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives having antiviral activity, represented by formula [I]: STR1 wherein B represents a base selected from the group consisting of purine, azapurine and deazapurine, which may be substituted with halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, alkylamino, hydroxyl, hydroxyamino, aminoxy, alkoxy, mercapto, alkylmercapto, aryl, aryloxy or cyano; and R represents a hydrogen atom or a phosphoric acid residue, and to a process for the production and use thereof.
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
Production of purines via reductive formylation
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, (2008/06/13)
In order to produce a purine of the general formula (I), STR1 in which R1 and R2 can be the same or different and denote H, OH, SH, NH2, N-(di)-alkyl, halogen, O-alkyl, S-alkyl, alkyl or aryl and alkyl represents an aliphatic residue with 1 to 4 carbon atoms and aryl represents a phenyl residue which is substituted if desired by CH3, OH, NH2 or halogen, from the corresponding 4-amino-5-nitrosopyrimidine of formula (II), STR2 in which R1 and R2 have the above-mentioned meaning, the compound of formula (II) is reductively formylated in a solvent at a temperature of 80° to 220° C. in the presence of formic acid and a catalyst based on a noble metal and the 4-amino-5-formylaminopyrimidine formed as an intermediate is cyclized.
4'-substituted nucleosides
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, (2008/06/13)
Nucleosides compounds of Formula I: STR1 wherein B is a purine or a pyrimidine; X and X' are H; Y is H; Y' is OH, F or H; or Y' and X' together makes a bond; Z is STR2 where n is zero, one, two or three; or Y' and Z together form a cyclic phosphate ester; Z' is --CN, --CH3, CH2 N3 or --CH2 J, where J is a halogen atom; or Z' and Y' together are --CH2 O--; and pharmaceutically acceptable esters, ethers, amides, N-acyl moieties and salts thereof.
