ORGN 612 |
| David R. Liu, Zev J. Gartner, Matthew W. Kanan, and Christopher T. Calderone. Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138 |
| Molecular evolution requires the translation of an amplifiable information carrier into the structures of the evolving molecules. An approach to the evolution of molecules other than proteins and nucleic acids uses DNA-templated synthesis as a method of translating DNA sequences into synthetic small molecules. We show that DNA-templated synthesis can direct a wide variety of powerful chemical reactions with high sequence-specificity and without requiring structural mimicry of the DNA backbone. The distance independence and sequence fidelity of DNA-templated synthesis allowed the simultaneous, one-pot translation of a model library of more than 1,000 templates into the corresponding thioether products, one of which was enriched by in vitro selection for protein binding and amplified by PCR. We also describe the development of general methods to enable the product of a DNA-templated reaction to undergo subsequent DNA-templated transformations, and have performed the first DNA-templated multi-step small molecule syntheses. Our findings set the stage for the in vitro evolution of synthetic small molecule libraries and provide experimental support for previously proposed hypotheses that nucleic acid-templated synthesis may have translated replicable information into some of the earliest functional molecules prior to the evolution of protein-based enzymes. |
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Nakanishi Prize
2:00 PM-4:40 PM, Wednesday, March 26, 2003 Convention Center -- La Nouvelle Ballroom A/B, Oral
Division of Organic Chemistry |