Combinatorial libraries

The Combinatorial Chemistry and Chemical Biology Shared Resource, or CCCBSR, provides combinatorial libraries and support services to UC Davis Comprehensive Cancer Center members. The one-bead one-compound, or OBOC, and the one-bead-two-compound, or OB2C, methods are highly efficient, both in compound synthesis and in library screening, and these ultra-high throughput methods are unmatched by any parallel synthesis methods. Many UC Davis investigators have developed successful grant proposals using these methods.

In addition to OBOC and OB2C libraries, the CCCBSR provides solution-phase small molecule libraries to comprehensive cancer center investigators.

One-bead-one and -two-compound combinatorial libraries

Dr. Kit S. Lam is the inventor of the one-bead one-compound, or OBOC, combinatorial library method. The OBOC library method is a powerful tool to discover ligands against various biological targets, such as protein kinase substrates and inhibitors, protease substrates and inhibitors, ligands for cell surface receptors, artificial enzymes and various ligands for the preparation of affinity column media.

Dr. Lam and co-workers have recently modified the OBOC method by adding a known cell-capturing ligand to the surface of every bead in the OBOC library to generate one-bead-two-compound, or OB2C, combinatorial libraries. In this method, each bead displays on its surface a cell-capturing molecule and a random library compound. When live cells are incubated with a OB2C library, the cell-capturing ligand directs the cells to attach to the bead surface, resulting in the display of random library molecules in proximity to the cell surface. Some of these library compounds interact with a cell surface receptor, resulting in specific biochemical or cellular response, which can be rapidly detected with an appropriate reporter system.

Cell surface receptors play important roles in cellular communication between adjacent cells, between cells and their extracellular microenvironment, and in intracellular signal transduction. Synthetic molecules that target these receptors are useful reagents for study of the biochemical pathways in which they are involved, and may even be used as lead compounds for the development of new drugs.

In situ releasable OBOC/OB2C solution-phase small molecule libraries

In situ releasable OBOC/OB2C solution-phase small molecule library technology involves the development of a novel polymer bead grafted with hydrophilic dendritic polymer on the bead surface for use in in situ solution-phase releasable assays. These compound-beads are placed in a single small dish containing microbead high-density micro-well arrays for ultrahigh-throughput solution-phase releasable assays. With this technology, a technician can screen over 100,000 chemical compounds in a few days. This OBOC chemical library method is relatively inexpensive and can be adapted to many existing cell-based or biochemical assays commonly used by many comprehensive cancer center members.