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Gas‐Phase Studies of Formamidopyrimidine Glycosylase (Fpg) Substrates
Author(s) -
Kiruba G. S. M.,
Xu Jiahui,
Zelikson Victoria,
Lee Jeehiun K.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201505003
Subject(s) - nucleobase , chemistry , dna glycosylase , kinetic isotope effect , ribose , gas phase , tautomer , dna , phase (matter) , isotope , stereochemistry , enzyme , kinetic energy , dna repair , biochemistry , organic chemistry , physics , deuterium , quantum mechanics
Gas‐phase thermochemical properties (tautomerism, acidity, and proton affinity) have been measured and calculated for a series of nucleobase derivatives that have not heretofore been examined under vacuum. The studied species are substrates for the enzyme formamidopyrimidine glycosylase (Fpg), which cleaves damaged nucleobases from DNA. The gas‐phase results are compared and contrasted to solution‐phase data, to afford insight into the Fpg mechanism. Calculations are also used to probe the energetics of various possible mechanisms and to predict isotope effects that could potentially allow for discrimination between different mechanisms. Specifically, 18 O substitution at the ribose O4′ is predicted to result in a normal kinetic isotope effect (KIE) for a ring‐opening “endocyclic” mechanism and an inverse KIE for a direct base excision “exocyclic” pathway.