Welcome to Chemical Biology in Translation (CBIT)
The Chemical Biology in Translation (CBIT) is directed by Dr. Scott Diamond and Dr. William DeGrado and provides resources in assay development, high throughput screening, hit confirmation, mechanism-of-action studies, docking, and medicinal chemistry expansion of prioritized scaffolds. Request for Proposals (RFP) are broadly advertised each year to the biological research community for chemical biology targets suitable for HTS and chemistry optimization. Housed within the Penn Center for Molecular Discovery (http://www.seas.upenn.edu/~pcmd), CBIT is fully instrumented for robotic screening in 96, 384, and 1536-well plates. Screening campaigns can involve biochemical, cellular, or model organism targets. Assay formats can include FI, TRF, FRET, FP, chemiluminescence, bioluminescence, alphaScreen, intracellular calcium, as well as cellular imaging based high content screening (HCS). Staff is available with experience in diverse systems such as proteases, kinases, reductases, polymerases, ligases, yeast, malaria, C. albicans, platelets, and mammalian cells. Chemical Resources: Specialized chemical libraries include: LOPAC, NINDS, Prestwick collection, 10K diversity set, 50K diversity set, and 50K Celera set.
The CBIT staff will advise interested scientists in the underlying principles of HTS assay design and optimization. With the proper selection of assay format, the assay provider can demonstrate the dynamic range of the assay in 96-well plate and obtainment of Z'>0.6 (a critical parameter to assay the quality of the assay signal and feasibility of HTS). The CBIT staff will work with the assay scientist to miniaturize the HTS protocol to work in the 384- or 1536-well plate formation ("assay implementation"). All hits are scored and subjected to dose-response analysis prior to confirmation in secondary tests run by the assay provider. With primary and secondary confirmation of activity, resynthesis and expansion of the scaffold is then possible.
The group also focuses medicinal chemistry and structural biology on one or two targets at any given time when an intense effort is appropriate.
Contact Information:Dr. Scott L. Diamond
Director, Penn Center for Molecular Discovery
Institute for Medicine and Engineering
University of Pennsylvania
Philadelphia, PA 19104