A primary goal of City of Hope's Comprehensive Cancer Center and its research programs is to develop new, more effective and less toxic therapies for the treatment of cancer. The Drug Discovery and Structural Biology (DDSB) Core was established to provide the necessary technical and scientific resource to facilitate drug discovery efforts consistent with the cancer center’s translational research goals. An important focus of the DDSB is on cancer drug discovery in the area of molecular-targeted therapeutics, as well as chemical biology probes. The core was established with these goals in mind and therefore is highly diverse in its services, yet highly convergent in its efforts. The core comprises 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.
For example, the high throughput screening component of the DDSB provides unique opportunities for discovering small-molecule inhibitors of targeted proteins. Next, lead compounds can be elaborated through medicinal chemistry and structure activity relationship studies. Once a good lead compound is developed, X-ray crystallographic analysis of the drug-protein complex begins. This is an essential component of any drug development process, since a detailed structural analysis is critical to understanding the drug-protein interaction and facilitates the optimization of ligand binding by molecular design. The general capabilities of the DDSB 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 complex molecule synthesis as well as the synthesis of small-molecule agonists and antagonists, imaging agents, affinity ligands, nanoparticles and focused combinatorial libraries. These compounds are used for mechanistic studies in chemical biology, generation of lead compounds for drug discovery, drug optimization for preclinical evaluation and, ultimately, 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. The synthetic component of the DDSB works closely with the new Chemical GMP Synthesis Facilities in developing good manufacturing practice synthesis processes for investigational new drug submissions. The other significant aspect of the DDSB lies in the structural characterization of drug-protein complexes by X-ray crystallography and other biophysical techniques such as surface plasmon resonance, isothermal titration calorimetry, and analytical ultracentrifugation. This unique transdisciplinary core enables development of new molecularly-targeted compounds for chemical biology studies and cancer therapies to enhance our translational research mission of the City of Hope Comprehensive Cancer Center. The goal of developing targeted molecular cancer therapeutics within various research programs of the cancer center is greatly facilitated through the newly-expanded, integrated DDSB facility.
Any subcomponent of the DDSB can be utilized on a stand-alone basis for a specific application. Please contact the co-directors or managers at the links below for more information on usage, pricing and availability.
David Horne, Ph.D.
626-256-4673, ext. 67310