Cell-free assay technologies for the identification of active compounds

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The cell-free assay development project encompasses this section's efforts in taking basic science discoveries from Center for Cancer Research researchers and evaluating specific experimental results to determine if these results can be utilized to develop high throughput screens and then developing those screens. The result of these efforts is the development of high throughput screens robust enough to tolerate natural product samples and sufficiently predictive to guide the identification and purification of bioactive compounds for continued experimentation and pre-clinical development. Specific Aim 1: The preliminary evaluation of thermodynamic and/or kinetic data from macromolecule-ligand interactions, the assessment of source and purity of potential assay reagents and, where warranted, production of protein reagents. Specific Aim 2: Bioassay development to adapt experimental methods to 384-well plate-based screening technologies, modification of these methods to allow the screening natural product samples. Specific Aim 3: Collaboration with the MTP Assay Development and Screening Section to automate and validate HTS compatible protocols for cell-free assay systems and establish criteria to assess quality of the resultant data and identification of active samples. Specific Aim 4: The development of suitable secondary and tertiary assay systems and development of chemical and biological criteria, in collaboration with the MTP Natural Products Chemistry Section, with which to prioritize extracts for natural products chemistry efforts. Specific Aim 5: The continued characterization of pure compounds derived from MTP screens including kinetic and thermodynamic evaluation, and biochemical mechanism of action studies.