Overview of Operations:
The major operations of the MLSMR include:
- the identification and acquisition of small molecule compounds;
- the application of a standard quality control regimen;
- handling, storing and maintaining the compound collection within established guidelines;
- distributing compound plates to the MLPCN centers; and
- depositing compound structures into PubChem.
Identification and Acquisition of Compounds:
In coordination with the External Scientific Advisory Committee and the Molecular Libraries Probe Production Center Network Steering Committee, the MLSMR develops compound selection criteria (i.e., stability, solubility, availability of sufficient quantities, ease of re-supply or re-synthesis, diversity) appropriate for the Molecular Libraries Probe Production Center Network collection. After approval by the NIH Molecular Libraries Project Team, the recommended criteria are used to identify compounds from commercial, academic, and government sources. Sets of proposed compounds are then sent to the External Scientific Advisory Committee and the NIH Project Team for review and selection of compounds approved for acquisition.
The MLSMR processes all samples it has received in a standard, high-throughput Quality Control (QC) regimen; one that checks for weight, solubility, identity, and purity. Sample weight is verified to ensure that the minimum amount required was received. Sample solubility in DMSO is checked and only completely soluble samples are accepted into the MLSMR. LC-MS is used to determine sample identity and purity. MLSMR accepts samples where the molecular ion is identified and Area Under the Curve (AUC) is at least 90% by Evaporative Light Scattering (ELS) or UV detection. In addition to QC of incoming samples, ongoing analysis of approximately 10% of the collection is conducted annually to monitor stability over time. [For more information about the handling and storage procedures adopted by the MLSMR, please see the following web page: http://mlsmr.evotec.com/MLSMR_HomePage/quality.html
Compound Handling, Storage and Distribution:
The MLSMR immediately stores samples that pass QC tests in automated storage equipment for fast retrieval. MLSMR uses a three-tier storage system: 1) Long Term Store, 2) Working Store, and 3) Short Term Store. The MLSMR stores the bulk sample dry in glass vials as the Long Term Store. Working Store samples of each compound are created in a 10 mM DMSO solution to be stored and used for approximately one year. The Working Store samples are in turn used to create microtiter plates to be shipped to the MLPCN, which are then held in the Short Term Store until shipment to the MLPCN (typically less than one week). Compounds are stored at -20°C in all three tiers of the storage system and all DMSO solutions are stored and handled under nitrogen atmosphere to prevent water absorption and ensure optimal stability and purity. [For more information about the handling and storage procedures adopted by the MLSMR, please see the following Web page: http://mlsmr.evotec.com/MLSMR_HomePage/storage.html]
Deposition of Compound Structures into PubChem:
Structures of all compounds in the MLSMR are deposited into PubChem, a public sector cheminformatics database of small organic molecules and their biological activities managed by the National Center for Biotechnology Information (NCBI). The Molecular Libraries Probe Production Centers will link to these substances when depositing HTS data (e.g., this includes data on the biological activities from HTS assays generated by the MLPCN) into PubChem. To access data on the structures of compounds in the MLSMR collection click on the previous link or search the PubChem Substance records using the keyword “MLSMR.”