Drug Discovery and Structural Biology
A primary goal of City of Hope's Comprehensive Cancer Center (CCC), and of its research programs, is to develop new, more effective, and less toxic therapies for the treatment of cancer. Thanks to extraordinary resources and brilliant minds, that goal is today more achievable than ever.
The Drug Discovery and Structural Biology (DDSB) Core was established to both technically and scientifically facilitate drug discovery efforts consistent with the translational research goals of the CCC. Two important points of focus for the DDSB, then, are chemical biology probes and discovery of cancer drugs in the area of molecular-targeted therapeutics.
Because the DDBS Core was established with these complex goals in mind, its services are impressively diverse but also highly convergent. The Core is comprised of four major service components: high throughput screening, biopolymer synthesis, small molecule synthesis and X-ray crystallography. These disciplines work together in a complementary and cohesive manner to provide a full array of early-phase drug discovery services and chemical probes for biological systems.
The high throughput screening component of the DDSB, for example, provides unique opportunities for the discovery of small-molecule inhibitors of targeted proteins. Following such discoveries, lead compounds can then be elaborated through medicinal chemistry and structural activity relationship studies. Once a good lead compound is developed in such a case, X-ray crystallographic analysis of the drug-protein complex begins. This analysis is an essential component of any drug development process, since its observations are critical to an understanding of drug-protein interaction and facilitates the optimization of ligand binding by molecular design.
The general capabilities of the DDSB Core are significant and include the design and synthesis of highly specialized biopolymers, including siRNA-aptamers, DNA-peptide hybrid derivatives, and peptides >100 amino acids in length. In addition, the Core maintains expertise in synthetic organic chemistry and is capable of synthesizing complex molecules as well as small-molecule agonists and antagonists, imaging agents, affinity ligands, nanoparticles, and focused combinatorial libraries. These compounds are used for mechanistic studies in chemical biology, in generation of lead compounds for drug discovery, in drug optimization for preclinical evaluation, and, ultimately, in the development of new targeted cancer therapeutics.
The DDSB is capable of synthesizing all structural classes, from small to large organic molecules, including air- and light-sensitive materials. Additionally, the synthetic component of the DDSB works closely with the new Chemical GMP Synthesis Facilities in developing good manufacturing practice synthesis processes for investigations of new drug submissions.
Another significant aspect of the DDSB lies in the structural characterization of drug-protein complexes by X-ray crystallography and by other biophysical techniques, such as surface plasmon resonance, isothermal titration calorimetry, and analytical ultracentrifugation.
The unique transdisciplinary core at the DDSB enhances the translational mission of the CCC by enabling development of new molecularly targeted compounds for chemical biology studies and for cancer therapies. The goal of developing targeted, molecular cancer therapeutics within various research programs within the cancer center is greatly facilitated through the newly-expanded, integrated DDSB facility.
Any subcomponent of the DDSB can be used on a stand-alone basis for a specific application. Please contact the co-directors or managers at the links below for more information on use, pricing, and availability.
626-256-4673, ext. 67310
626-256-HOPE (4673), ext. 60227