Triplex formation involving 2',4'-BNA with isoquinolone base analogue: efficient and selective recognition of C:G interruption.

We examined the thermodynamic properties of 2',4'-bridged nucleic acid containing 1-isoquinolone as a nucleobase (QB) to recognize a C interruption in the homopurine strand of the target duplex for pyrimidine motif triplex formation at neutral pH. The triplex formation involving triplex-forming oligonucleotide with QB is highly sequence-selective to specifically recognize C:G target base pair rather than the other G:C, T:A, or A:T base pairs. QB.C:G triad gives significantly larger binding constant than T.C:G triad, which has been known to be the most stable combination in natural base.C:G triad. Our results certainly support the idea that QB could be a key nucleoside to recognize a C interruption in the homopurine strand of the target duplex with high binding affinity and selectivity, and reduce the restriction of target sequences for triplex formation.