Multistep small-molecule synthesis programmed by DNA templates.
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.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Zev J
ZJ
Gartner
Matthew W
MW
Kanan
David R
DR
Liu
D000577:Amides / Q000138:chemical synthesis*; D004247:DNA / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*; D013698:Templates, Genetic
D000577:Amides; D009841:Oligonucleotides; D010455:Peptides; D004247:DNA