Rapid screening of binding constants by calibrated competitive 1H NMR spectroscopy

Chemistry : a European Journal
Richard E HeathDavid K Smith

Abstract

A calibrated competitive NMR method has been developed that is appropriate for the rapid screening of binding constants. This method involves the initial characterisation of a receptor-substrate binding event for which the (1)H NMR spectrum of a given receptor (calibrant) is modified by the substrate of interest at a range of concentrations. For all subsequent "unknown" receptors, K(a) values are then determined by using a competition assay (in the presence of the calibrant receptor) by measuring a single standard (1)H NMR spectrum. This enables a rapid assessment of the recognition properties of a library of potential receptors. Only the calibrant receptor needs to be NMR active, while the library of putative receptors, as well as the substrate, can be NMR silent. This method assumes the formation of complexes of 1:1 stoichiometry. To demonstrate this methodology, the binding of a number of crown ether type compounds with K+ ions has been studied. Comparison of the binding strengths obtained by using this approach with those in the literature shows excellent agreement. A range of new compounds that have recently been synthesised within our group has also been screened in order to illustrate how this approach can rapidly assess...Continue Reading

Citations

Jun 9, 2004·Current Opinion in Chemical Biology·Natarajan Srinivasan, Jeremy D Kilburn
Aug 12, 2015·ACS Combinatorial Science·Filip UlatowskiJanusz Jurczak
Oct 11, 2016·Analytical Chemistry·Yaewon KimChristian Hilty
Oct 1, 2015·Organic & Biomolecular Chemistry·Filip UlatowskiJanusz Jurczak
Feb 24, 2015·Angewandte Chemie·Yaewon Kim, Christian Hilty
Mar 13, 2019·Chemical Society Reviews·Stephanie A BoerNicholas G White
Jun 13, 2006·Chemical Communications : Chem Comm·Feihe HuangHarry W Gibson
Apr 25, 2006·Organic & Biomolecular Chemistry·Keith J WinstanleyDavid K Smith
Nov 30, 2004·Chemical Communications : Chem Comm·Feihe HuangMehdi Ashraf-Khorassani

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