Video: Kit Lam, co-director of the Combinatorial Chemistry Shared Resource at UC Davis Comprehensive
Cancer Center, describes how combinatorial library methods for drug discovery and basic cancer research.
Combinatorial library methods not only offer great potential for facilitating the drug discovery process but also provide powerful tools for basic research in various disciplines. These methods enable investigators to generate a large number of chemical compounds that can be used as valuable source for the discovery of drug leads, molecular imaging agents and capturing agents for molecular markers.
In the area of basic research, large collections of chemical compounds can be used to probe their effects on specific cellular function. Compounds that elicit or suppress a specific cellular response can then be identified and used as reagents to study cellular pathways involved in these cellular functions. This field of chemical genetics relies heavily on the availability of compound collections, which is difficult to find in academic laboratories.
NOTICE TO ALL PRINCIPAL INVESTIGATORS
This resource is funded by the UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (NCI P30CA093373). Publications that have utilized facility resources, services or scientific data generated by the resource should acknowledge the resource or the assistance provided by resource staff and cite the NCI CCSG grant. The manuscript must comply with NIH Public Access Policy and therefore should be deposited in PubMed Central through the NIHMS system either through your publisher or self-upload. An electronic copy of the publication should also be sent to the resource directors.
Dr. Lam is the inventor of the one-bead one-compound (OBOC) combinatorial library method, and through the Combinatorial Chemistry Shared Resource he has been providing OBOC combinatorial libraries and support services to Cancer Center members. The OBOC method is highly efficient, both in compound synthesis and in library screening. Indeed, it is the ultra-high throughput method unmatched by any parallel synthesis methods. Many UC Davis investigators have developed successful grant proposals using this method.
In addition to OBOC libraries, the Combinatorial Chemistry Shared Resource has been providing solution-phase small molecule libraries to Cancer Center investigators. The technology involves the development of a novel polymer bead grafted with hydrophilic dendritic polymer on the bead surface such that these beads can be used for in situ solution-phase releasable assays. We can place compound-beads in a single small dish containing microbead high-density micro-well arrays for ultrahigh-throughput solution-phase releasable assays. Over 100,000 chemical compounds can be screened by a technician in a few days. More importantly, this OBOC chemical library method is relatively inexpensive and can be adapted to many existing cell-based or biochemical assays commonly used by many of our Cancer Center members.