City of Hope's primary goal for its comprehensive cancer center and translational research is to develop more effective and less toxic new therapies for cancer treatment.
To support this mission, we established the Drug Discovery and Structural Biology (DDSB) core to facilitate drug discovery efforts technically and scientifically.
The DDSB's unique transdisciplinary services and expanded, integrated space enable the development of new molecular-targeted compounds for chemical biology studies and cancer therapies.
The core comprises four major service components:
- High throughput screening
- Synthetic biopolymer chemistry
- Small molecule synthesis
- 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 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 understanding drug-protein interaction and facilitate 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 and 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 the 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 can synthesize 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 Chemical GMP Synthesis core 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 other biophysical techniques, such as surface plasmon resonance, isothermal titration calorimetry and analytical ultracentrifugation.
Any subcomponent of the DDSB can be used on a stand-alone basis for a specific application.
In a given year, City of Hope conducts more than 400 clinical trials enrolling more than 6,000 patients.
City of Hope is focused on basic and clinical research in cancer, diabetes and other life-threatening diseases.