Structure and Biophysics for a Six Letter DNA Alphabet that Includes Imidazo12-a-135-triazine-2(8H)-4(3H)-dione (X) and 24-Diaminopyrimidine (K)

摘要

A goal of synthetic biology is to develop new nucleobases that retain the desirable properties of natural nucleobases at the same time as expanding the genetic alphabet. The non-standard Watson-Crick pair between imidazo[1,2-a]-1,3,5-triazine-2(8H)-4(3H)-dione (>X) and 2,4-diaminopyrimidine (>K) does exactly this, pairing via complementary arrangements of hydrogen bonding in these two nucleobases, which do not complement any natural nucleobase. Here, we report the crystal structure of a duplex DNA oligonucleotide in B-form including two consecutive >X:K pairs in GATC>XKDNA determined as a host-guest complex at 1.75 Å resolution. >X:K pairs have significant propeller twist angles, similar to those observed for A:T pairs, and a calculated hydrogen bonding pairing energy that is weaker than that of A:T. Thus, although inclusion of >X:K pairs results in a duplex DNA structure that is globally similar to that of an analogous G:C structure, the >X:K pairs locally and energetically more closely resemble A:T pairs.