Parallel Synthesis and Biocatalytic Amplification of Marine-Inspired Libraries: An Integrated Approach Toward Discovering New Chemotherapeutics
Abstract
We have made further progress toward preparing lead compounds for new anticancer drugs from a novel class of starting materials containing the cyclopentenone scaffold. These compounds are inspired by natural products with proven anti-cancer and anti-viral activities. We have prepared parallel library #2 through a variation of the general chemical methodology that was used to prepare library #1 (see last year's report). This new cyclopentenones comprise a library of complex, polyfunctional organic molecules of unprecedented structure. The most important class of enzymes for biocatalytic amplification of these compounds is the cytochrome P450s. We have developed new reaction systems (e.g., surfactant-stabilized microemulsions and hydrogel-entrapped enzymes in organic solvents) that will expand the synthetic utility of cytochrome P450s and render them much more effective catalysts for structural elaboration of the chemically synthesized compounds. We have also begun to screen our libraries against several cell lines including solid tumor, leukemia, and normal cells. Combining combinatorial synthesis with biocatalytic amplification of chemical libraries is a new approach to drug discovery, which we are applying to a promising but largely unexplored class of compounds. Even if we do not identify a new clinical candidate, it is. becoming increasingly likely that we will identify lead compounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA444016
Entities
People
- Douglas S Clark
Organizations
- University of California, Berkeley