CONTACT

Leibniz-Institut für Molekulare Pharmakologie (FMP)Med-Genomhaus (Geb.87, 3.OG) / Robert-Roessle-Str. 10, 13125 Berlinwww.fmp-berlin.de/screening_unit.html / www.chembionet.info

• Dr. Jens Peter von Kries / Screening Unit T +49 (0)30 9406 -2982 / F +49 (0)30 9406 -2922 / kries@fmp-berlin.de• Dr. Edgar Specker / Compound Management T +49 (0)30 9406-3064 / F +49 (0)30 9406-2948 / specker@fmp-berlin.de • Dr. Ronald Frank / Coordinator EU-OPENSCREEN T (mobile) +49(0)178 2844481 / F +49 (0)30 9406-2948 / frank@fmp-berlin.de• Ronald Kühne / Drug Design / kuehne@fmp-berlin.de

Screening UnitScreening Unit

AUTOMATED DATA PROCESSINGHigh-throughput screening campaigns generate a large amount of data which must be analysed in a fast and effi cient way. The basis for the automated analysis of screening data is standard operating procedures (SOPs) defi ned for each experi-mental setup. In-house software devel-oped by our Drug Design Group permits a complete analysis of screening data, allowing documentation of the raw data, statistical evaluation after data normaliz-ation, identifi cation of hits, and automated reporting for customers. This automated reporting system creates an exhaustive pdf report. The report con-tains the hit list, graphical representations for quality controls (normal distributions, signal stability, z‘-factor lists), and the heat maps of all plates depicting the z-scores of the measured samples as a col-

our representation on every position of the microtiter plate. These representations are suitable for the detection of measure-ment artefacts.

EU-OPENSCREEN Ronald Frank

As the co-ordinator of EU-OPENSCREEN, the FMP has initiated a Europewide network of screening platforms such as the Screening Unit. With EU support, the FMP coordinates the development of this network with the aim of making academic drug discovery accessible across Europe. All data gener-ated from the projects that these facilities support are fed into a European database that will provide the foundation for future research.

384tip pipetting systems enable to test up to 20.000 compounds per day for biological effects.

SCREENING TECHNOLOGIES

Using state-of-the-art technologies, scien-tists at the Screening Unit analyse the eff-ects of up to 20,000 compounds in a single day, depending on the type of assay used.

The Screening Unit offers the following ass-ays for the discovery of qualifi ed probes.

• Automated microscopes for high content screening (HCS)• Highly sensitive impedance measure ments with living cells• Capillary electrophoresis assays for kinases and phosphatases in microfl uidic chips • Plate readers for measurements of pro- tein-protein interactions (AlphaScreen & Fluorescence polarization)• Chemical library microarrays for rapid identifi cation of protein binders

In addition, the FMP offers fragment-based screening using the latest NMR-technol-ogy, another focus of FMP research.(Hartmut Oschkinat)

DRUG DESIGNRonald Kühne

DESIGN OF SCREENING LIBRARIESSuccess in small molecule screening reliesheavily on the preselection of a library of potent-ially bioactive compounds from a much wider, virtually unlimited range of molecules integ-rating the collected knowledge of Medicinal Chemistry. For the purpose of a central screen-ing facility serving totally different types of assays and target families, it is a particular challenge to reach an adequate coverage of chemical space. In order to address this task, the Drug Design Group of the FMP developed in-house library design software using an inno-vative fragment-based concept. Our concept is based on a defi ned number of fragments (privileged substructures) which were selected by a genetic algorithm anal-ysing the MDL Drug Data Report (MDDR) and the World Drug Index (WDI) to identify most common substructures in biologically active compounds. In combination with our in-house ADMET and reactivity fi lters and our database of commercially available compounds, we are able to effi ciently upgrade our screening library as well as to build hitbased focused libraries.

 

SCREENING UNIT Jens von Kries

In 2003, the Leibniz-Institut für Molekulare Pharmakologie (FMP) established the Screen-ing Unit – a state-of-the-art screening plat-form for the discovery of compounds as quali-fi ed probes to be used as new tools for basicresearch in biology. The unit affords open access to biologists and chemists and has already supported more than 100 projects from researchers throughout Europe and the USA.

COMPOUND MANAGEMENT Edgar Specker

The Screening Unit manages the central compound collection of the Chemical Biol-ogy Network (ChemBioNet), an initiative of biologists and chemists from academic re-search institutes in Europe. The collection currently comprises about 60,000 com-pounds stored in automated REMP storage freezers. The library is continually expand-ed with new collections of synthetic and natural compounds donated by chemical research groups. Data integrity of the com-pounds is secured by automated software analysis with Pipeline Pilot, and quality control is provided with LC-MS analyses.

Robotic manipulator places 96-tube rack on cap removing module.

Cytotoxic potential of compounds identifi ed by fl uorescent staining of cellular structures. Light blue nuclei mark cells with damaged membranes, while red fl uorescence marks functional mitochodria.