title: Rapid characterization of folding and binding interactions with thermolabile ligands by DSC.
abstract: Differential scanning calorimetry (DSC) is a powerful technique for measuring tight biomolecular interactions. However, many pharmaceutically relevant ligands are chemically unstable at the high temperatures used in DSC analyses. Thus, measuring binding interactions is challenging because the concentrations of ligands and thermally-converted products are constantly changing within the calorimeter cell. Using experimental data for two DNA aptamers that bind to the thermolabile ligand cocaine, we present a new global fitting analysis that yields the complete set of folding and binding parameters for the initial and final forms of the ligand from a pair of DSC experiments, while accounting for the thermal conversion. Furthermore, we show that the rate constant for thermolabile ligand conversion may be obtained with only one additional DSC dataset.
authors: Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal QC H3A 0B8, Canada. anthony.mittermaier@mcgill.ca.
authors: R W
authors: RW
authors: Harkness
authors: Department of Chemistry, York University, 4700 Keele Street, Toronto ON M3J 1P3, Canada.
authors: S
authors: S
authors: Slavkovic
authors: Department of Chemistry, York University, 4700 Keele Street, Toronto ON M3J 1P3, Canada.
authors: P E
authors: PE
authors: Johnson
authors: Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal QC H3A 0B8, Canada. anthony.mittermaier@mcgill.ca.
authors: A K
authors: AK
authors: Mittermaier