title: Enthalpy array analysis of enzymatic and binding reactions.
abstract: Enthalpy arrays enable label-free, solution-based calorimetric detection of molecular interactions in a 96-detector array format. The combination of the small size of the detectors and the ability to perform measurements in parallel results in a significant reduction of sample volume and measurement time compared with conventional calorimetry. We have made significant improvements in the technology by reducing the temperature noise of the detectors and improving the fabrication materials and methods. In combination with an automated measurement system, the advances in device performance and data analysis have allowed us to develop basic enzyme assays for substrate specificity and inhibitor activity. We have also performed a full titration of 18-crown-6 with barium chloride. These results point to future applications for enthalpy array technology, including fragment-based screening, secondary assays, and thermodynamic characterization of leads in drug discovery.
authors: Scripps-PARC Institute for Advanced Biomedical Sciences, Palo Alto Research Center, 3333 Coyote Hill Rd., Palo Alto, CA 94304, USA. mrecht@parc.com
authors: Michael I
authors: MI
authors: Recht
authors: Dirk
authors: D
authors: De Bruyker
authors: Alan G
authors: AG
authors: Bell
authors: Michal V
authors: MV
authors: Wolkin
authors: Eric
authors: E
authors: Peeters
authors: Greg B
authors: GB
authors: Anderson
authors: Anand R
authors: AR
authors: Kolatkar
authors: Marshall W
authors: MW
authors: Bern
authors: Peter
authors: P
authors: Kuhn
authors: Richard H
authors: RH
authors: Bruce
authors: Frank E
authors: FE
authors: Torres
mesh_terms: D001331:Automation / Q000295:instrumentation; D017609:Barium Compounds / Q000378:metabolism; D002151:Calorimetry / Q000295:instrumentation / Q000379:methods*; D002712:Chlorides / Q000378:metabolism; D043844:Crown Ethers / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D004798:Enzymes / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D040081:Protein Array Analysis / Q000295:instrumentation / Q000379:methods; D011485:Protein Binding; D013379:Substrate Specificity; D013816:Thermodynamics; D017186:Titrimetry; D014361:Trypsin Inhibitors / Q000378:metabolism / Q000494:pharmacology
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D043844:Crown Ethers; D004791:Enzyme Inhibitors; D004798:Enzymes; D014361:Trypsin Inhibitors; C024986:barium chloride; C015762:18-crown-6; D006593:Hexokinase