1463-10-1Relevant articles and documents
SYNTHESIS AND ANTIVIRAL ACTIVITY OF 1-(&β-D-ARABINOFURANOSYL)THYMINE
Kvasyuk, E. I.,Kulak, T. I.,Tkachenko, O. V.,Mikhaylopulo, I. A.,Zinchenko, A. I.,et al.
, p. 493 - 496 (1989)
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High-yielding cascade enzymatic synthesis of 5-methyluridine using a novel combination of nucleoside phosphorylases
Visser, Daniel F.,Rashamuse, Konanani J.,Hennessy, Fritha,Gordon, Gregory E.R.,Van Zyl, Petrus J.,Mathiba, Kgama,Bode, Moira L.,Brady, Dean
, p. 245 - 253 (2010)
A novel combination of Bacillus halodurans purine nucleoside phosphorylase (BhPNP1) and Escherichia coli uridine phosphorylase (EcUP) has been applied to a dual-enzyme, sequential, biocatalytic one-pot synthesis of 5-methyluridine from guanosine and thymine. A 5-methyluridine yield of >79% on guanosine was achieved in a reaction slurry at a 53 mM (1.5% w/w) guanosine concentration. 5-Methyluridine is an intermediate in synthetic routes to thymidine and the antiretroviral drugs zidovudine and stavudine.
General Principles for Yield Optimization of Nucleoside Phosphorylase-Catalyzed Transglycosylations
Kaspar, Felix,Giessmann, Robert T.,Hellendahl, Katja F.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
, p. 1428 - 1432 (2020)
The biocatalytic synthesis of natural and modified nucleosides with nucleoside phosphorylases offers the protecting-group-free direct glycosylation of free nucleobases in transglycosylation reactions. This contribution presents guiding principles for nucleoside phosphorylase-mediated transglycosylations alongside mathematical tools for straightforward yield optimization. We illustrate how product yields in these reactions can easily be estimated and optimized using the equilibrium constants of phosphorolysis of the nucleosides involved. Furthermore, the varying negative effects of phosphate on transglycosylation yields are demonstrated theoretically and experimentally with several examples. Practical considerations for these reactions from a synthetic perspective are presented, as well as freely available tools that serve to facilitate a reliable choice of reaction conditions to achieve maximum product yields in nucleoside transglycosylation reactions.
17O NMR of Nucleosides. 3 - Chemical Shifts of Substituted Uridines and Ribothymidines
Schwartz, Herbert M.,MacCoss, Malcolm,Danyluk, Steven S.
, p. 885 - 894 (1985)
Uridine and ribothymidine derivatives, bearing different substituents at C-5 and enriched (Ca 50percent) with 17O in the O-4 and O-2 carbonyls, have been studied via 17O NMR in both acetonitrile and aqueous solvents.The solvent shift differences between acetonitrile and water at O-4 (30-42 ppm) and O-2 (13-16 ppm) vary significantly from each other, but the chemical shift changes induced by changing the substituent at C-5 correlated well only with the O-4 shifts and the electron-withdrawing ability of the substituent.Examination of the 17O shifts of model compounds reconfirms the predominance of keto tautomers for both carbonyls.The significance of the solvent shifts and substituent shifts are discussed with respect to the electronic structure of the nucleoside base rings, and with respect to the hydrogen-bonding abilities of the carbonyl groups.Other nucleoside derivatives studied include those in which the 17O enrichment is in the ring linking the base to the sugar moiety in a pyrimidine cyclonucleoside, in the sugar hydroxy groups and in the phosphodiester linkage of a highly strained ring system in a nucleoside cyclic monophosphate.
A catalytic method for chemoselective detritylation of 5′-tritylated nucleosides under mild and heterogeneous conditions using silica sulfuric acid as a recyclable catalyst
Khalafi-Nezhad, Ali,Parhami, Abolfath,Soltani Rad, Mohammad Navid,Zolfigol, Mohammad Ali,Zare, Abdolkarim
, p. 5219 - 5222 (2007)
A rapid, mild and highly efficient procedure for the chemoselective deprotection of triphenylmethyl (trityl, Tr), p-anisyldiphenylmethyl (monomethoxytrityl, MMT) and di-(p-anisyl)phenylmethyl (dimethoxytrityl, DMT) groups from nucleoside trityl ethers has been established. The deprotection was achieved at room temperature, using a catalytic amount of silica sulfuric acid (SSA) in acetonitrile. The trityl nucleosides were deprotected in 2-17 min without any depurination. These conditions are compatible with other acid sensitive hydroxyl protecting groups such as p-methoxybenzyl (PMB), isopropylidene, cyclohexylidene, di-(p-anisyl)methylidene, triisopropylsilyl (TIPS) and t-butyldimethylsilyl (TBDMS).
Stabilization of Escherichia coli uridine phosphorylase by evolution and immobilization
Visser, Daniel F.,Hennessy, Fritha,Rashamuse, Justice,Pletschke, Brett,Brady, Dean
, p. 279 - 285 (2011)
Mutation and immobilization techniques were applied to uridine phosphorylase (UP) from Escherichia coli in order to enhance its thermal stability and hence productivity in a biocatalytic reaction. UP was evolved by iterative saturation mutagenesis. Compared to the wild type enzyme, which had a temperature optimum of 40 °C and a half-life of 9.89 h at 60 °C, the selected mutant had a temperature optimum of 60 °C and a half-life of 17.3 h at 60 °C. Self-immobilization of the native UP as a Spherezyme showed a 3.3 fold increase in thermostability while immobilized mutant enzyme showed a 4.4 fold increase in thermostability when compared to native UP. Combining UP with the purine nucleoside phosphorylase from Bacillus halodurans allows for synthesis of 5-methyluridine (a pharmaceutical intermediate) from guanosine and thymine in a one-pot transglycosylation reaction. Replacing the wild type UP with the mutant allowed for an increase in reaction temperature to 65 °C and increased the reaction productivity from 10 to 31 g l-1 h -1.
Use of nucleoside phosphorylases for the preparation of 5-modified pyrimidine ribonucleosides
Alexeev, Cyril S.,Drenichev, Mikhail S.,Dorinova, Evgeniya O.,Esipov, Roman S.,Kulikova, Irina V.,Mikhailov, Sergey N.
, (2019/11/13)
Enzymatic transglycosylation, a transfer of the carbohydrate moiety from one heterocyclic base to another, is catalyzed by nucleoside phosphorylases (NPs) and is being actively developed and applied for the synthesis of biologically important nucleosides. Here, we report an efficient one-step synthesis of 5-substitited pyrimidine ribonucleosides starting from 7-methylguanosine hydroiodide in the presence of nucleoside phosphorylases (NPs).
