Zev J. Gartner; David R. Liu
J. Am. Chem. Soc., 2001, 123, 6961-6963
https://doi.org/10.1021/ja015873n

Abstract

Despite their limited chemical functionality, proteins and nucleic acids dominate the solutions to many complex chemical problems because they can be evolved through iterated cycles of diversification, selection, and amplification. Researchers have demonstrated extensively that proteins and nucleic acids initially lacking desired activities can be mutated, amplified, and reselected to afford evolved molecules with greatly enhanced properties. We are interested in creating amplifiable and evolvable libraries of non-natural small molecules by developing methods to translate DNA into synthetic structures. Achieving this goal requires using DNA to direct chemical reactions sequence-specifically in a manner much more general than has been reported thus far. Researchers have previously demonstrated the ability of nucleic acid templates to promote the coupling of adjacently annealed oligonucleotides to form nucleic acids and nucleic acid analogues. We hypothesized that the proximity effect provided by DNA-templated synthesis can be used to generate libraries of synthetic small molecules unrelated in structure to the DNA backbone in one-pot, parallel reactions.