Expansion of the genetic alphabet with an unnatural base pair is a long-standing goal of synthetic biology. We have developed a class of unnatural base pairs, formed between d5SICS  and analogues of dMMO2  , that are efficiently and selectively replicated and transcribed. In an effort to further characterize and optimize replication, we report the synthesis and evaluation of more than twenty new dMMO2  analogues bearing different substituents designed to be oriented into the developing major groove. In addition, we describe the synthesis and analysis of the ribo- and deoxyribo-variants, (d)5SICS  and (d)MMO2  , modified with propargylamine linkers that allow for the site-specific modification of DNA or RNA during or after enzymatic synthesis. Finally, we reveal the structural basis for the polymerase recognition of a predominantly hydrophobic unnatural base pair.   

Expansion of the genetic alphabet: Optimization and applications of an unnatural base pair

243rd National Meeting (2012)

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