University of Cambridge > Talks.cam > Chemistry Departmental-wide lectures > NEW ADVANCES IN ISOTHERMAL TITRATION CALORIMETRY: GOING FAR BEYOND TRADITIONAL ANALYSIS WITH AFFINIMETER

NEW ADVANCES IN ISOTHERMAL TITRATION CALORIMETRY: GOING FAR BEYOND TRADITIONAL ANALYSIS WITH AFFINIMETER

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Isothermal Titration Calorimetry (ITC) is a physical technique, essential in the field of molecular recognition. It is widely used in academic research laboratories and also in the pharmaceutical industry where it is used right through the initial steps of hit validation and lead optimization of drug discovery programs1.

Traditionally, ITC offers a direct and quantitative measure of the binding affinity (KA), enthalpy (ΔH) and stoichiometry and for this it has been long considered the gold standard for quantitative measurements of biomolecular interactions. But the battery of information potentially available from ITC goes far beyond the thermodynamic profiling of binding events. A proper analysis of ITC data registered under optimized experimental conditions can yield rich thermodynamic and structural information that contributes to the elucidation of structure activity relationships (SAR) and mechanistic aspects of interactions. Besides, the kinetic profiling can be readily determined from standard ITC thermograms and the method KinITC, as these are a measure of the heat change occurred upon titrant injection over time2. Until recently, the main hurdles to exploit the full potential of ITC was not in the experimental facet but in the data analysis step.

Herein we bring to the fore that the combination of technical improvements in ITC equipment, together with novel analytical tools like those incorporated in the software AFFIN Imeter, is now letting to exploit the full potential of the technique. This is illustrated with selected examples of ITC analyses of challenging ligand-receptor interactions of interest.

This talk is part of the Chemistry Departmental-wide lectures series.

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