Journal
SCIENCE
Volume 305, Issue 5690, Pages 1601-1605Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1102629
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Funding
- NIGMS NIH HHS [R01 GM065865-04, R01 GM065865, R01 GM065865-01A2, R01 GM065865-02, R01 GM065865-03, R01GM065865] Funding Source: Medline
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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.
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