Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Iglesias, Luis E.; Lewkowicz, Elizabeth Sandra; Médici, Rosario; Bianchi, Paola; Iribarren, Adolfo M.

doi:10.1016/j.biotechadv.2015.03.009

Cited by 60 publications

(36 citation statements)

References 174 publications

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“…Synthetic compounds of this type are of interest for instance in the development of antivirals and anticancer agents. [172][173][174] A triazole unit can be employed to either derivatize or entirely replace the nucleobase moiety, or it may be appended to the base or to the sugar unit, to afford a nucleoside analogue. Subsequent phosphorylation also provides access to nucleotides.…”

Section: Nucleoside and Nucleotide Analoguesmentioning

confidence: 99%

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

et al. 2016

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The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry and the construction of 2 electronic devices. This review discusses the mechanism, scope and applications of the RuAAC reaction, covering the literature during the last 10 years. CONTENTS

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Section: Nucleoside and Nucleotide Analoguesmentioning

confidence: 99%

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

et al. 2016

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“…On the contrary, the salvage pathway is composed by a group of reutilization routes by which the cell can satisfy its purine requirements from endogenous and/or exogenous sources of preformed purines. In this regard, numerous enzymes from purine salvage pathway have become valuable catalysts for mono or multi-enzymatic synthesis of nucleosides and nucleotides, such as nucleoside kinases (NKs) [12][13][14][15], phosphoribosyltransferases [7,[9][10][11], nucleoside phosphorylases [4,8,16,17], 2′-deoxyribosyltransferases [5,[18][19][20], among others.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Multi-Enzymatic Production of Purine Derivatives with Application in Pharmaceutical and Food Industry

et al. 2018

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Abstract:Biocatalysis reproduce nature's synthetic strategies in order to synthesize different organic compounds. Natural metabolic pathways usually involve complex networks to support cellular growth and survival. In this regard, multi-enzymatic systems are valuable tools for the production of a wide variety of organic compounds. Methods: The production of different purine nucleosides and nucleoside-5 -monophosphates has been performed for first time, catalyzed by the sequential action of 2 -deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) and hypoxanthine-guanine-xanthine phosphoribosyltransferase from Thermus themophilus HB8 (TtHGXPRT). Results: The biochemical characterization of LdNDT reveals that the enzyme is active and stable in a broad range of pH, temperature, and ionic strength. Substrate specificity studies showed a high promiscuity in the recognition of purine analogues. Finally, the enzymatic production of different purine derivatives was performed to evaluate the efficiency of multi-enzymatic system LdNDT/TtHGXPRT. Conclusions: The production of different therapeutic purine nucleosides was efficiently catalyzed by LdNDT/TtHGXPRT. In addition, the resulting by-products were converted to IMP and GMP. Taking all of these features, this bioprocess entails an efficient, sustainable, and economical alternative to chemical synthetic methods.

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“…Due to this, the use of PRTs as therapeutic targets has been extensively reported (el Kouni 2003). In contrast, only a few examples about their use as catalysts in NMP synthesis has been described (Scism et al 2007(Scism et al , 2010Valino et al 2015;Iglesias et al 2015;Esipov et al 2016;Hansen et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…According to their substrate specificity, purine PRTs are classified into two general classes: 6-aminopurine PRTs (APRT), strictly specific for 6-aminopurines, such as adenine and 6-aminopurine derivatives (Craig and Eakin 2000;Iglesias et al 2015;Esipov et al 2016), and 6-oxopurine PRTs (HPRT, GPRT, XPRT, HGPRT, XGPRT or HGXPRT) that can recognize different kinds of 6-oxopurines, such as hypoxanthine, guanine, xanthine and other 6-oxopurine analogs (el Kouni 2003;Craig and Eakin 2000;Scism et al 2007;Scism & Bachmann 2010;Iglesias et al 2015;Valino et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Cloning, expression and biochemical characterization of xanthine and adenine phosphoribosyltransferases fromThermus thermophilusHB8

Arco

Martínez

Donday

et al. 2017

Biocatalysis and Biotransformation

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Purine phosphoribosyltransferases, purine PRTs, are essential enzymes in the purine salvage pathway of living organisms. They are involved in the formation of C-N glycosidic bonds in purine nucleosides-5 0 -monophosphate (NMPs) through the transfer of the 5-phosphoribosyl group from 5-phospho-a-D-ribosyl-1-pyrophosphate (PRPP) to purine nucleobases in the presence of Mg 2þ . Herein, we report a simple and thermostable process for the one-pot, one-step synthesis of some purine NMPs using xanthine phosphoribosyltransferase, XPRT or adenine phosphoribosyltransferase, APRT2, from Thermus thermophilus HB8. In this sense, the cloning, expression and purification of TtXPRT and TtAPRT2 is described for the first time. Both genes, xprt and aprt2 were expressed as his-tagged enzymes in E. coli BL21(DE3) and purified by a heat-shock treatment, followed by Ni-affinity chromatography and a final, polishing gel-filtration chromatography. Biochemical characterization revealed TtXPRT as a tetramer and TtAPRT2 as a dimer. In addition, both enzymes displayed a strong temperature dependence (relative activity >75% in a temperature range from 70 to 90 C), but they also showed very different behaviour under the influence of pH. While TtXPRT is active in a pH range from 5 to 7, TtAPRT2 has a high dependence of alkaline conditions, showing highest activity values in a pH range from 8 to 10. Finally, substrate specificity studies were performed in order to explore their potential as industrial biocatalyst for NMPs synthesis. ARTICLE HISTORY

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Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Cited by 60 publications

References 174 publications

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

One-Pot Multi-Enzymatic Production of Purine Derivatives with Application in Pharmaceutical and Food Industry

Cloning, expression and biochemical characterization of xanthine and adenine phosphoribosyltransferases fromThermus thermophilusHB8

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