Novel isosorbide-based substrates for human butyrylcholinesterase

J. F. Gilmer, M. N. Lally, P. Gardiner, G. Dillon, J. M. Gaynor, S. Reidy

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Butyrylcholinesterase [EC 3.1.1.8] present widely in mammalian tissue does not have a precisely defined biological function or known endogenous substrate. However, it plays an important role in the detoxification of certain xenobiotics and is an established vector for the systemic liberation of other drugs from their prodrugs. While investigating a series of isosorbide-based prodrugs, we discovered that BuChE catalyses the hydrolysis of esters of the simple sugar isosorbide with unusually rapidity and in some cases with remarkable regioselectivity. In this study, a series of isosorbide esters were synthesised and their rates of hydrolysis measured by HPLC following incubation in diluted plasma solution. In general, little hydrolysis of the 5-ester group could be observed but the 2-ester group was usually hydrolysed very rapidly and the hydrolysis rate exhibited an unusual dependence on the identity of the 5-group. The results indicate that while the 5-ester group is not itself hydrolysed it is important for productive binding in isosorbide diesters.

Original languageEnglish
Pages (from-to)317-319
Number of pages3
JournalChemico-Biological Interactions
Volume157-158
DOIs
Publication statusPublished - 15 Dec 2005

Keywords

  • Butyrylcholinesterase
  • Human plasma
  • Isosorbide esters
  • Substrate

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