Synthesis and enzymatic evaluation of the guanosine analogue 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG): insights into the phosphorolysis reaction mechanism based on the blueprint transition state: SN1 or S N2?

A modified experimental procedure for the synthesis of MESG (2-amino-6-mercapto-7-methylpurine ribonucleoside) 1 has been successfully performed and its full characterization is presented. High resolution ESI(+)-MSMS indicates both the nucleoside bond cleavage as the main fragmentation in the gas ph...

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Bibliographic Details
Published in:Journal of the Brazilian Chemical Society 2010, Vol.21 (1), p.151-156
Main Authors: Neto, Brenno A. D., Lapis, Alexandre A. M., Netz, Paulo A., Spencer, John, Dias, Silvio L. P., Tamborim, Silvia M., Basso, Luiz A., Santos, Diógenes S., Dupont, Jairton
Format: Article
Language:English
Subjects:
CHEMISTRY, MULTIDISCIPLINARY
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Summary:A modified experimental procedure for the synthesis of MESG (2-amino-6-mercapto-7-methylpurine ribonucleoside) 1 has been successfully performed and its full characterization is presented. High resolution ESI(+)-MSMS indicates both the nucleoside bond cleavage as the main fragmentation in the gas phase and a possible S N1 mechanism. Ab initio transition state calculations based on the blue print transition state support this mechanistic rationale and discard an alternative S N2 mechanism. Assays using purine nucleoside phosphorylase (PNP) enzyme (human and M. tuberculosis sources) indicate its efficiency in the phosphorolysis of MESG and allow the quantitative determination of inorganic phosphate in real time assay.
ISSN:0103-5053
1678-4790
DOI:10.1590/S0103-50532010000100022