Parallel-stranded DNA: Enhancing duplex stability by the 'G-clamp' and a pyrrolo-dC derivative

The new pyrrolo-dC derivative 4 tethered with an alkylamino side chain via a triazole linker was synthesized. Oligonucleotides containing the G-clamp 3 or the pyrrolo-dC derivative 4 were prepared. Oligonucleotide synthesis and deprotection under standard conditions led to unwanted side product formation. The side product was identified as an acrylonitrile adduct of the aminoalkyl side chain. Changing the synthesis and work-up conditions to fast-deprotection chemistry and performing beta-elimination of the cyanoethyl group on the solid support yielded pure oligonucleotides. Oligonucleotide duplexes with parallel chain orientation were constructed incorporating dA.dT and isoG(d).dCbase pairs. Replacement of dC-residues by the G-clamp 3 led to extraordinarily stable duplexes (Delta T-m = +11 degrees C for two incorporations) in ps DNA, while the pyrrolo-dC derivative 4 behaved like dC. Surprisingly, the G-clamp 3 forms an even more stable base pair with 2'-deoxyisoguanosine in DNA with parallel chain orientation than with 2'-deoxyguanosine in aps DNA.