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. 2001 Jan 26;3(Suppl A):L005. doi: 10.1186/ar153

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

M Auer 1
PMCID: PMC3273231

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.

References

  1. Fluorescence correlation spectroscopy: Lead discovery by miniaturized HTS.
  2. Auer M, Moore Keith J, Meyer-Almes F-J, Guenther R, Pope AJ, Stoeckli KA. Drug Discovery Today, 1998. pp. 457–465. [DOI]
  3. Auer M, Gstach H. Fluorescent dyes (AIDA) for solid phase and solution phase screening. United States Patent, WO 00/37448.
  4. Meyer-Almes FJ, Auer M. 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. Biochemistry. 2000;39(43):13261–13268. doi: 10.1021/bi000057y. [DOI] [PubMed] [Google Scholar]
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  6. Bühler C, Stöckli K, Auer M. Review in press: Fluorescence Spectroscopy: Valeur/Brochon, Trends in Fluorescence Spectroscopy (Springer Verlag, 2001)

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