Core Facility

Edgar Specker

Compound Management

Portrait

The aim of the Core Facility Compound Mangement is the production of screening plates for the primary screening at the Screening Unit, the preparation of hitpicking plates in order to conduct concentration-dependent validations of primary hits, the QC-controls of these hits and the support of users to prioritize their hit lists.


Profile

The goal of the core facility is the provision of screening plates to the Screening Unit and the preparation of hitpicking plates to conduct concentration-dependent validations of hits. It performs the QC-controls and helps the user to prioritize the hit lists. It manages a diversity library of 43.000 compounds enriched with 4.000 fragments, an academic library of 8.000 compounds and 20.000 natural product derived compounds.

 

About the Facility

The Compound Management was initiated in 2010 to facilitate the access for the academic community to a state-of-the-art compound management facility and was upgraded over the last decade. Initially, it started as an integral part of the Screening Unit and the Medicinal Chemistry group before it became an independent Core Faciltiy in 01/2020. At first, a REMP storage system hosted a compound library of 37.000 compound. Due to the higher demand of the constantly growing commercial and academic libraries an upgrade to the automated KIWI storage system was required with a larger capacity of 110.000 compounds. Today, it manages a diversity library of 43.000 compounds and a fragment library of 4000 compounds purchased from different commercial vendors. Over the years a academic library of about 8000 compounds was collected from a huge variety of academic chemistry groups together with 20.000 natural product derived compounds from Analyticon Discovery GmbH. In 2019, it moved next to the laboratories of the EU-OPENSCREEN ERIC where both infrastructures will benefit from each other using theirs synergies while maintaining their different strategic and scientific operations. The ultimate goals of the Core Facility is the provision of screening plates for the primary screening at the Screening Unit, the preparation of hitpicking plates in order to conduct concentration-dependent validations of primary hits, the QC-controls of these hits and the support of users to prioritize their hit lists. 

Compound Management

The Compound Management manages the central compound collection of the FMP using a Liconic-KIWI storage systems combined with a FreedomEvo pipetting system (Tecan).  The collection is extended by donations of academic chemists, 4000 biology-annotated compounds (Selleck library) and a natural product collection of 20.000 cpds from AnalytiCon Discovery which assembles a smart library collections of 75.000 compounds ready to screen. The automated storage system provides a capacity of about 110.000 cpds with a total number of 220.000 tubes stored at -20° C. The Compound Management actively collects compound collections from academic chemists and currently holds about 8.000 unique donated cpds.
The collection of commercially available compounds has been financed by the FMP in cooperation with the Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch (MDC), the Helmholtz-Zentrum für Infektionsforschung (HZI), and the University of Konstanz. The design and selection of compounds is based on a maximum common substructure analysis of the World Drug Index (WDI).
The project-oriented chemical synthesis and optimization of small molecules is supported by medicinal chemists, drug modellers and structural biologists at the Institute on the basis of individual cooperations.

Tecan Evoware Workstation

This Freedom EVO provides a worktable containing a hotel to thaw frozen compound solutions in DMSO, a robotic arm (RoMa) for  transport of 96-tube racks (Remp) or 384well plates, liquid handling tools for 96-tip transfer (MCA) and a flexible 8 needle tool (LiHa for transfer of DMSO to solubilize compound powders or for hit picking). Furthermore wash stations for cleaning the liquid handling modules are placed on the worktable and a de-capper for removing Remp caps before liquid transfer. A 2D barcode reader controls racks and tubes (barcodes at bottom). A heat sealer is used for sealing 384-well plates with an aluminium foil to generate screening replicates. All modules of the Evoware platform are covered into a hood to prevent contaminations.

KIWI Store (220.000 tubes)

The KIWI Store (LiCONiC AG) offer fully automated storage and retrieval of compounds with a total number of 220.000 tubes organized in 96-tube racks. The tubes contain 200 µl DMSO solutions for each compound at  concentrations of 10 mM in DMSO. Individual tubes are identified by a 2D-barcode at bottom and the racks by 1D-barcodes. The provided technology enables individual sample access and manipulation by simply pushing the tube through the source rack to an empty destination rack.
The automated selection of individual tubes in the -20°C freezer also offers the benefits of minimizing freeze/thaw cycles, library cleaning and compression, and avoiding oxidation and water uptake. This is especially important for the unique compounds donated from academic chemists and protects the long term storage. Furthermore this technology enables  for generation of target specific sub libraries .The software tracks the samples at all stages and allows them to be chosen for retrieval from imported sample lists or queries. After samples are picked in the -20 °C environment they are delivered in delivery racks for further processing. The delivery rack is returned to the KIWI Store and the software automatically updates the location of the rack inside the store.

The KIWI Store

Dr. Martin Neuenschwander (Screening Unit) has developed a software environment allowing to combine the KIWI Store with the Freedom EVO liquid handling workstation, creating a fully automated liquid handling and sample management platform. 
Together, the Freedom EVO and the KIWI Store can be used to automate a variety of sample logistic tasks for compound management and screening. The task of hit picking from 200 µl Remp tube racks (96 tube racks, last column empty tubes) and generation of screening replicates (384well plates, last two columns empty) are running in routine. Furthermore work lists with compound weights (as powders) and molecular weight data automatically drive the liquid handling module for transfer of calculated DMSO volumes to create identical concentrations of compounds in each of 88 glass vials for transfer into 96tube

LC-MS Agilent TOF

The Agilent 6220 Accurate-Mass TOF LC/MS system provides mass analyses for profiling, identifying, characterizing, and quantifying low molecular-weight compounds and biomolecules.
The TOF system delivers MS analyses that supports applications such as impurity testing, product degradation studies. We use the automated sample uptake and analysis system to validate 352 hit compounds from a 384well MTP in a single run. Data for hit identity, integrity and purity are reported for up to 352 hit compounds.

Contact Office

Dajana Baudach

Secretary, Sun Group,
Secretary Nazaré Group


Research Section

Chemical Biology