The CMLD Core facility has three integral components; the Library Production Core located on the University of Chicago campus, the Hit-to-Lead Development Resource located at Northwestern University, and the Computational Cheminformatics Core at the University of Illinois at Chicago.
All chemical libraries produced by the CMLD investigators are subjected to mass-guided HPLC purification. The Library Production Core is located at the University of Chicago and provides the equipment and the personnel, which is devoted for this time-consuming task. High purity of small-molecule libraries is critical to minimizing the number of false-positive hits in HTS assays. The Library Generation Core provides resources to enable rigorous analysis of analytical purity of each compound produced in the CMLD facility.
The long-term stability of compound libraries prepared by CMLD is ensured by storage of all compound libraries in the ultra-low temperature freezers at -86°C in neat form, as well as in aliquoted DMSO stock solutions in a 96-well plate format.
Discovery of new bioactive compounds is the ultimate objective of high-throughput synthesis. Such discovery can only be enabled if large collections of new drug-like compounds can be produced in an efficient manner. In addition to submission of CMLD libraries to the NIH Molecular Libraries Small-Molecule Repository, our chemical libraries will be made available for screening in many individual biology laboratories.
A critical step that follows biological screening is the ability to evaluate the resulting small-molecule “hits” and develop them further into useful reagents for basic biomedical research and drug discovery. This is an important and often-missed link in the area of chemical biology and academic drug discovery efforts. The Hit-to-Lead Resource of our Center is located at Northwestern University and provides unique support for advancing initial hits into useful tools for chemical biology and new leads for drug discovery.
This component of the CMLD Core is located at the University of Illinois at Chicago and has several important functions. It provides database system for storing compounds by their chemical structures using multiple representations to facilitate convenient retrieval and comparison. In addition, we are working on integrating different descriptors and computational tools for effective similarity search in the diversity subspace projected using novel descriptors that are selected based on their effectiveness. Furthermore, this component of the center develops effective QSAR models that relate chemical, biochemical, and physiological effects of compounds with their computed molecular properties projected in the descriptor space.