DNA-templated organic synthesis and selection of a library of macrocycles.
The translation of nucleic acid libraries into corresponding synthetic compounds would enable selection and amplification principles to be applied to man-made molecules. We used multistep DNA-templated organic synthesis to translate libraries of DNA sequences, each containing three "codons," into libraries of sequence-programmed synthetic small-molecule macrocycles. The resulting DNA-macrocycle conjugates were subjected to in vitro selections for protein affinity. The identity of a single macrocycle possessing known target protein affinity was inferred through the sequence of the amplified DNA template surviving the selection. This work represents the translation, selection, and amplification of libraries of nucleic acids encoding synthetic small molecules rather than biological macromolecules.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Zev J
ZJ
Gartner
Brian N
BN
Tse
Rozalina
R
Grubina
Jeffrey B
JB
Doyon
Thomas M
TM
Snyder
David R
DR
Liu
D000577:Amides; D019921:Biotinylation; D003062:Codon; D003500:Cyclization; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D015723:Gene Library; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000302:isolation & purification; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000577:Amides; D003062:Codon; D006573:Heterocyclic Compounds, 1-Ring; D009838:Oligodeoxyribonucleotides; C032239:fumaramide; D004247:DNA