Glycosyl conformational and inductive effects on the acid catalysed hydrolysis of purine nucleosides.

Abstract:

:The log kobs vs. pH profiles were determined in the intermediate acidity region for the glycosyl hydrolysis of guanosine and its 8-amino, 8-monomethylamino, 8-dimethylamino and 8-bromo derivatives. The decreased rate of the 8-amino and enhanced rate of the 8-bromo compound compared to guanosine support an A type mechanism: base protonation followed by glycosyl bond cleavage. All three 8-amino guanosines exhibited log kobs - pH profiles clearly showing that both mono and di-base protonated nucleosides undergo hydrolysis. The 700 fold rate acceleration of 8-N(CH3)-guanosine compared to 8-NHCH3-guanosine and the 110 fold rate acceleration of 8-N(CH3)2-adenosine compared to 8-NHCH3-adenosine could be unequivocally attributed to the fixed syn glycosyl conformation of both 8-dimethylamino compounds and relief of steric compression upon hydrolysis in these molecules. The lack of anomerization of all substrates during the course of the reaction supports an A rather than a Schiff-base mechanism.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Jordan F,Niv H

doi

10.1093/nar/4.3.697

subject

Has Abstract

pub_date

1977-03-01 00:00:00

pages

697-709

issue

3

eissn

0305-1048

issn

1362-4962

journal_volume

4

pub_type

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