ORGN 673 |
| DNA-programmed chemistry provides the foundation of an integrated platform for synthesis and identification of compounds with desired functional properties. We present a description of the integrated system, with results from the synthesis, characterization, and selection of drug-like compound libraries. Synthetic oligonucleotides are designed to program the stepwise combinatorial assembly of complex (>10e3) small molecule libraries in a single pot. At each synthetic step, the full library mixture is characterized by high-resolution time-of-flight LCMS, enabling the highly parallel synthesis to be tracked at a level comparable to single-reactions. Following assembly, each compound remains attached to the unique DNA strand which programmed its synthesis, enabling functional evaluation of the library as a mixture in microliter-scale solution-phase binding assays. High throughput hybridization and sequencing allows analysis of a broad dynamic range of binders, directly providing structure-activity information in selection experiments. Finally, we discuss unique methods to direct DNA-programmed libraries toward specific molecular targets. |
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Lipids, Nucleotides, and Mimetics
1:00 PM-4:40 PM, Wednesday, 13 September 2006 Moscone Center -- Room 131, Oral
Division of Organic Chemistry |