A nonpolar aromatic nucleoside derivative based on 2,4-difluorotoluene
(F), a non-hydrogen bonding shape analog of thymidine, was recently shown
to be replicated against adenine with high efficiency and fidelity. This led
to the suggestion that geometric matching, potentially even in the absence
of hydrogen bonding between bases in a pair, may be sufficient to direct nucleotide
selection during replication. We have examined the solution structure of the
F−A pair in the context of a 12 base pair DNA duplex. We find that,
despite the destabilization caused by this analog, the F−A pair very
closely resembles that of a TA pair in the same context. This lends
support to the importance of shape matching in replication.
A pair in the same context. This lends
support to the importance of shape matching in replication.
