A new modified cytosine base capable of base pairing with guanine using four hydrogen bonds

Oligonucleotides, containing 4-N-(1H-pyrrol-2-ylcarbonyl)deoxycytidine (dC^Pyc) and related derivatives, were synthesized via deprotection using 1.5 M NaOMe/MeOH. Among them, oligodeoxynucleotides containing dC^Pyc exhibited a higher hybridization affinity for DNA and RNA than the unmodified oligodeoxynucleotides. Comparative analysis between dC^Pyc and its derivatives by molecular dynamic simulation indicated that the C^Pyc residue could form four hydrogen bonds with the opposite G nucleobase keeping a more planar structure than the C^Inc residue where the Pyc group was replaced with a 1H-indol-2-ylcarbonyl group.