The integration of functional genomics, combinatorial chemistry and nanotechnology into a miniaturized drug discovery process

ar153 ARJ Meeting abstract The integration of functional genomics, combinatorial chemistry and nanotechnology into a miniaturized drug discovery process Auer M

Novartis Forschungsinstitut GmbH, Dermatology, Fluorescence based HTS-Technology Program, Vienna, Austria

Arthritis Res 21st European Workshop for Rheumatology Research Meeting abstracts 21st European Workshop for Rheumatology Research Vienna, Austria

1–4 March 2001

1465-9905 2001 3 Suppl A L005 10.1186/ar153 15 1 2001 26 1 2001 2001 2001 BioMed Central Ltd ar-3-2-l005

Future concepts in miniaturized HTScreening technologies will concentrate on making optimal use of the two emerging technologies, combinatorial chemistry and functional genomics. To effectively exploit compounds from highly-parallel combinatorial synthesis and the high number of new target proteins from functional genomics, Novartis and Evotec BioSystems developed the CONA-BSP (confocal nanoscanning - bead scanning picking technology) as a novel high throughput - low hit-rate HTS process. In combination with the Novartis proprietary AIDA-Technology, quantitative on-bead confocal fluorescence screening can be combined with off-bead confirmation via a series of fluorescence techniques such as fluorescence anisotropy, or rotational correlation time applied to equilibrium binding studies.

Single molecule fluorescence spectroscopy and confocal nanoscanning/AIDA technology provide an optimal combination for a miniaturized automated uHTS process with high mechanistic resolution in functional and coupled assay systems.

Fluorescence correlation spectroscopy: Lead discovery by miniaturized HTS. Auer M Moore J Keith Meyer-Almes F-J Guenther R Pope AJ Stoeckli KA Drug Discovery Today, 1998 3 457 465 10.1016/S1359-6446(98)01240-9 Auer M Gstach H Fluorescent dyes (AIDA) for solid phase and solution phase screening. United States Patent, WO 00/37448 Enzyme inhibition assays with fluorescence correlation spectroscopy: A new algorithm for the derivation of kcat/Km and Ki values at substrate concentrations lower than the Michaelis Menten constant. Meyer-Almes FJ Auer M Biochemistry 2000 39(43) 13261 13268 10.1021/bi000057y The integration of single molecule detection technologies into miniaturized drug screening: Current status and future perspectives. Bühler C Stöckli K Auer M Review in press: Fluorescence Spectroscopy: Valeur/Brochon, Trends in Fluorescence Spectroscopy (Springer Verlag, 2001)