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Feb 26, 2007
 |  BioCentury  |  Tools & Techniques

Big and small of DNA chemistries

Making pharmaceutically relevant chemical libraries remains an important bottleneck in drug discovery. Two DNA-directed chemistry companies that were founded in the past two years are creating very different kinds of libraries that serve different purposes.

Both Ensemble Discovery Corp. and Vipergen ApS are using DNA-based chemistry to catalyze reactions and synthesize compounds, which allows for more complex molecules to be assembled in less time and with greater control than conventional chemistry methods allow.

Ensemble has created small, focused libraries of about 20,000 complex molecules, called macrocycles. Vipergen is betting that the fidelity of its technique will allow it to build bigger and bigger libraries - up to 1012 compounds - that will yield greater chemical diversity without sacrificing quality.

Both technologies begin with multiple unique short complementary DNA strands, each attached to a different chemical moiety. DNA hybridizes at very low concentrations, thus chemical moieties attached to them are forced into close proximity, which causes them to react, when normally they would not.

These DNA-directed techniques also allow multiple reactions to proceed independently in the same mixture, while chemists traditionally perform each reaction sequentially in separate vessels.

The process also can be used to direct stepwise reactions that can generate compounds of progressively greater complexity.

At the back end of their processes, both companies use the DNA sequences that directed the reactions as tags, so PCR and sequencing can be used to identify compounds that give a positive signal in affinity screening.

Where the two companies’ technologies differ most from each other is in the DNA architecture used to synthesize the molecules (see...

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