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PubMed · 15700999

DNA-templated functional group transformations enable sequence-programmed synthesis using small-molecule reagents.

Kaori Sakurai·Thomas M Snyder·David R Liu
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Abstract

DNA-templated organic synthesis (DTS) has previously been used primarily to direct coupling reactions between two DNA-linked reactants. In some cases, reactants are difficult or impossible to tether to DNA oligonucleotides. The development of strategies that enable non-DNA linked small-molecule reagents to participate in sequence-programmed synthesis therefore would significantly expand the capabilities of DTS. We developed efficient DNA-templated functional group transformations of template-linked azides into corresponding amines, carboxylic acids, and thiols. The application of these reactions to a single-solution mixture of four template-linked organic azides enabled each azide to be transformed sequence specifically into a sulfonamide, carbamate, urea, or thiourea using small-molecule sulfonyl chloride, chloroformate, isocyanate, or isothiocyanate reagents not tethered to DNA. Only the four desired products were observed, without formation of any of the 12 possible undesired cross-products. Our results represent a new approach to small molecule diversification in a DNA-programmed manner.

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AminesAzidesCarbamatesCarboxylic AcidsChemistry, OrganicDNAElectrophoresis, Polyacrylamide GelOligonucleotidesSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSulfhydryl CompoundsSulfonamidesThioureaUreaJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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Kaori Sakurai, Thomas M Snyder, David R Liu. 2005-02-16. DNA-templated functional group transformations enable sequence-programmed synthesis using small-molecule reagents.. https://doi.org/10.1021/ja0432315

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