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

UFRGS, Porto Alegre, Brazil¹  Netz, Paulo A.¹  Spencer, John¹  Universidade Federal do Pampa, Bagé, Brazil¹  University of Brasilia, Brasilia, Brazil¹  Santos, Diógenes S.¹  Neto, Brenno A. D.¹  Dupont, Jairton¹  Dias, Silvio L. P.¹  Basso, Luiz A.¹  PUC, Porto Alegre, Brazil¹  Tamborim, Silvia M.¹  Lapis, Alexandre A. M.¹  University of Greenwich at Medway, UK¹ 

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

DOI  :  10.1590/S0103-50532010000100022

学科分类：化学（综合）

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 SN1 mechanism. Ab initio transition state calculations based on the blue print transition state support this mechanistic rationale and discard an alternative SN2 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】

Unknown