Intracellular metabolism of 2′,3′-dideoxynucleosides in duck hepatocyte primary cultures

Kitos, Theresa E.; Tyrrell, D. Lorne

doi:10.1016/0006-2952(95)00052-2

Cited by 10 publications

(7 citation statements)

References 42 publications

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“…dDAPR was also obtained using thymidine as substrate and Proteus vulgaris as biocatalyst (88%, 0.5 h, 45°C). The use of dDAPR as deoxyguanosine prodrug in L1210 cells (Weckbecker and Cory, 1987) and in ducks (Kitos and Tyrrell, 1995) was reported. ddDAPR is a potent and selective inhibitor of HIV and HBV and moreover, a strong inhibitor of human ADA.…”

Section: As Nucleoside Prodrugsmentioning

confidence: 96%

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Iglesias

Lewkowicz

Médici

et al. 2015

Biotechnology Advances

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Section: As Nucleoside Prodrugsmentioning

confidence: 96%

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Iglesias

Lewkowicz

Médici

et al. 2015

Biotechnology Advances

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“…Since 2,6-diaminopurine nucleosides can also be deaminated in vivo by animal and human ADA [159,160] to produce guanosine analogues, they are also used as prodrugs.…”

Section: B Nucleoside Synthesismentioning

confidence: 99%

Nucleoside Phosphorylases

Lewkowicz

Iribarren

2006

COC

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Nucleoside phosphorylases (NPs) are transferases that catalyse the reversible cleavage of the glycosidic bond of ribo-or deoxyribo nucleosides, in the presence of inorganic phosphate, to generate the base and ribose-or deoxyribose-1-phosphate.Since pyrimidine as well as purine nucleoside phosphorylases exist, the combination of both enzymes makes possible the generation of purine nucleosides from pyrimidine ones. As a consequence, NPs from different sources, mainly bacterial, have been exploited as tools for the enzymatic synthesis of nucleoside analogues. These molecules are extensively used as antiviral and anticancer agents because of their ability to act as reverse transcriptase inhibitors or chain terminators in RNA or DNA synthesis.This review covers literature reports from 2000 on, focused mainly on the synthesis of nucleosides by free and immobilised microbial whole cells, along with some examples of modified nucleosides obtained by coupling transglycosylation to other enzymatic reactions.The biological aspects of NPs are also discussed since they became an interesting target for clinical applications due to their key role in nucleotide metabolism. Finally, brief comments about their structures and catalytic mechanisms are included.

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“…Using selected ion monitoring, the characteristic profiles of 3TC and its phosphorylated forms, 3TCMP, 3TCDP, and 3TCTP, are clearly displayed. The concentration of 3TCTP in the cell is estimated to be , 10 28 M. The sodium ion plug and the phosphate anions plug signals were verified with standards. Figure 7 presents the mass spectrum of 3TCTP obtained from a fullscan on-line CE-MS analysis.…”

Section: Phosphorylation Of 3tc In Hep G2 Cell Linesmentioning

confidence: 99%

“…It is important to determine the antiviral ddNs and their phosphorylated forms for basic pharmacological studies. High-performance liquid chromatography (HPLC) with UV [6][7][8], radioactivity [3,[9][10][11], or mass spectrometry [12][13][14] detection has been commonly used for their analysis. HPLC with radioactivity detection is very sensitive, but entails the use of radioactive materials.…”

Section: Introductionmentioning

confidence: 99%

Capillary electrophoresis‐electrospray‐mass spectrometry of nucleosides and nucleotides: Application to phosphorylation studies of anti‐human immunodeficiency virus nucleosides in a human hepatoma cell line

Liu¹,

Huang

Tyrrell

et al. 2005

Electrophoresis

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We report the use of capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) for the determination of antiretroviral dideoxynucleosides (ddNs), their nucleotides, and a set of ribonucleosides and ribonucleotides. A CE system for separation of most commonly used antiretroviral ddNs has been developed based on a basic buffer with a volatile electrolyte suitable for ESI-MS detection in an untreated capillary column. Positive and negative ionization modes are investigated and compared for sensitive and stable electrospray performance. A 14-compound mixture of nucleosides and nucleotides is profiled in a single capillary zone electrophoresis separation with a distinct elution order: electroosmotic flow, ddNs, mononucleotides, dinucleotides, and trinucleotides in less than 18 min. The fragmentation pathways of the nucleosides and nucleotides in ESI-MS have been interpreted. Concentration limits of detection are 100 to 200 nM with an injection volume of approximately 10 nL. This technique has been used to detect naturally occurring nucleotides and to study the metabolism of lamivudine (3TC) in the human hepatoma cell line Hep G2. 3TC and its metabolites 3TC-monophosphate, 3TC-diphosphate, and 3TC-triphosphate were detected after 10 h of incubation of 3TC with the cells.

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Intracellular metabolism of 2′,3′-dideoxynucleosides in duck hepatocyte primary cultures

Cited by 10 publications

References 42 publications

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Nucleoside Phosphorylases

Capillary electrophoresis‐electrospray‐mass spectrometry of nucleosides and nucleotides: Application to phosphorylation studies of anti‐human immunodeficiency virus nucleosides in a human hepatoma cell line

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