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?

Journal of the Brazilian Chemical Society

Brenno A. D. Neto²  Alexandre A. M. Lapis¹  Paulo A. Netz¹  John Spencer¹  Silvio L. P. Dias¹  Silvia M. Tamborim¹  Luiz A. Basso¹  Diógenes S. Santos¹  Jairton Dupont¹ 

[1] ,University of Brasilia Laboratory of Medicinal and Technological Chemistry Brasilia DF ,Brazil

关键词: MESG;    PNP enzyme;    ESI;    tuberculosis;   

DOI  :  10.1590/S0103-50532010000100022

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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