Artificial Biology and Biomimetic Chemistry
The Meggers group has a longstanding interest in designing artificial
DNA-inspired duplexes with novel physicochemical properties. We recently
succeeded in designing an artificial glycol nucleic acid (GNA) with a
structurally much simplified backbone. In fact, the GNA backbone may be the
most atom economical solution for a functional nucleic acid backbone. It has
just three carbon atoms. That's a world record! Surprisingly, GNA forms
duplexes that are thermally far more stable than DNA or RNA duplexes of the
same sequence. Also, nucleotides can be synthesized conveniently just by
regioselective and stereospecific ring opening of glycidol and this allows
to access both enantiomers of GNA. This work has been recently featured in
Chemical & Engineering News.
Figure 7. Comparison of the constitutions of DNA, RNA, and
Eschenmoser's threofuranosyl nucleic acid (TNA) with our glycol nucleic acid
(GNA). Right: GNA duplex modeled by Prof. Jeff Saven's group.
Figure 8. Synthesis of GNA nucleotides with gT as an example.
We are currently applying novel metallo-base pairing schemes to this GNA, develop chemical and enzymatic replication of GNA, and evolve GNA with enzymatic activities. We are also following the question if GNA may have been a potential candidate for an anchestor of RNA in the evolution of life on Earth.