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J Am Chem Soc. 2002 Sep 4;124(35):10304-6.

Multistep small-molecule synthesis programmed by DNA templates.

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Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.


The translation of DNA sequences into synthetic products is a key requirement of our approach to evolving synthetic molecules through iterated cycles of translation, selection, and amplification. Here we report general linker and purification strategies for sequence-specific DNA-templated synthesis that collectively enable the product of a DNA-templated reaction to be isolated and to undergo subsequent DNA-templated reactions. Using these strategies, we have achieved the first multistep nucleic acid-templated small-molecule syntheses to generate two different molecules. In addition to representing a method for translating DNA templates sequence-specifically into corresponding multistep synthetic products, our findings also provide experimental support for previously proposed models invoking multistep nucleic acid-templated synthesis as mediating the prebiotic translation of replicable information into the earliest functional molecules.

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