Recent developments in isothermal titration calorimetry label free screening.
Isothermal titration calorimetry (ITC) is a label free technique used for direct detection of biological interactions by measurement of the heat given off or taken up during the reaction. In this article we will introduce the ITC technique and review two applications of ITC in drug discovery; small molecule/protein interactions and enzyme kinetics. We will also describe the characteristics of a new miniaturized, ultrasensitive calorimeter. This new microcalorimetry system reduces the quantity of protein (or other macromolecule sample) required to obtain a complete thermodynamic profile (n, K, DeltaH and DeltaS) by up to 7-fold. The reduction in required sample quantities allows ITC to be effectively utilized at earlier stages of the drug discovery and development process.
Peters
William B
WB
GE Healthcare, Products Group, MicroCal, 22 Industrial Drive East, Northampton, MA 01060, USA.
Frasca
Verna
V
Brown
Richard K
RK
D002151:Calorimetry / Q000295:instrumentation / Q000379:methods*; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D012260:Ribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013194:Staining and Labeling; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D004791:Enzyme Inhibitors; D008024:Ligands; D012260:Ribonucleases; D024402:Carbonic Anhydrase II