Title

Acid dissociation constants of uridine-5'-diphosphate compounds determined by 31phosphorus nuclear magnetic resonance spectroscopy and internal pH referencing

Document Type

Article

Publication Date

10-24-2012

Abstract

The acid dissociation constant (pKa) of small, biological molecules is an important physical property used for investigating enzyme mechanisms and inhibitor design. For phosphorus-containing molecules, the 31P nuclear magnetic resonance (NMR) chemical shift is sensitive to the local chemical environment, particularly to changes in the electronic state of the molecule. Taking advantage of this property, we present a 31P NMR approach that uses inorganic phosphate buffer as an internal pH reference to determine the pKa values of the imide and second diphosphate of uridine-5'-diphosphate compounds, including the first reported values for UDP-GlcNAc and UDP-S-GlcNAc. New methods for using inorganic phosphate buffer as an internal pH reference, involving mathematical correction factors and careful control of the chemical shift reference sample, are illustrated. A comparison of the newly determined imide and diphosphate pKa values of UDP, UDP-GlcNAc, and UDP-S-GlcNAc with other nucleotide phosphate and thio-analogs reveals the significance of the monosaccharide and sulfur position on the pKa values. © 2012 Elsevier B.V.

Publication Source (Journal or Book title)

Analytica Chimica Acta

First Page

63

Last Page

69

This document is currently not available here.

COinS