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DNA-Templated Organic Synthesis
Matthew Coulter
Organic-Biological Seminar
Department of Chemistry
University of Toronto
February 4, 2008
DNA-Templated Organic Synthesis
David R. Liu
Professor of Chemistry and Chemical Biology
Harvard University
• Small molecule library synthesis
• DNA assisted reaction discovery
2
DNA-Templated Synthesis
Transcription
Translation
DNA Protein
DNA Synthetic compound 3
DNA-Templated Organic Synthesis
Conventional Screening Approach DNA-Templated-Approach
• spatial separation generally required • All molecules synthesized in one pot
• each compound analyzed individually • All molecules analyzed simultaneously
• adequate material required for screen • fmol - nmol scale
• workload increases with sample size • workload does not scale with sample size
• Synthetic compound library size
109 – 1013
• Modern high-throughput screening
facility
• 9 – 9000 years
• Tools: MS, NMR, HPLC etc. • Tools: molecular biology
4
Rozenman, M.M.; McNaughton, B.R., Liu, D.R. Curr. Opin. Chem. Biol. 2000, 11, 259-268.
Can DNA Encode Chemical Reactions?
Strategy: Link nucleophile and electrophile to separate strands of complementary DNA
Reagent
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