Over more than two decades, DNA-encoded libraries (DEL) have been developed as a novel tool for the pharmaceutical and biomedical research areas. Xiaoyu Li, Peking University, China, and colleagues have devised a DNA-templated synthetic method that lets them construct an entire DEL using just a single DNA template.
The usual approach uses one template for one compound. The new approach exploits the pairing promiscuity of “deoxyinosine”, a nucleotide base derived from inosinic acid. The team designed their “universal template” – shaped like a hairpin – by incorporating three deoxyinosines as anticodons, the deoxyinosines pair up indiscriminately with each of the four standard bases present in DNA, and so this template can hybridize with multiple DNAs composed of different codon sequences.
The team explains that a single DNA template can thus direct DNA-templated reactions with different reagent DNAs comprising different sequences. This simplifies the whole process of DEL production.
- Multistep DNA-Templated Synthesis Using a Universal Template
Yizhou Li, Peng Zhao, Mingda Zhang, Xianyuan Zhao, Xiaoyu Li
J. Am. Chem. Soc. 2013.