jo6b01498_si_001.pdf (3.28 MB)

7‑Deaza-2′-deoxyguanosine: Selective Nucleobase Halogenation, Positional Impact of Space-Occupying Substituents, and Stability of DNA with Parallel and Antiparallel Strand Orientation

Download (3.28 MB)
journal contribution
posted on 16.08.2016, 00:00 by Sachin A. Ingale, Frank Seela
The positional impact of phenyl or phenyltriazolyl residues on the properties of 7-deaza-2′-deoxyguanosine, such as fluorescence, sugar conformation, and stability in DNA and DNA-RNA double helixes was studied. To this end, regioselective iodination protocols were developed for 7-deaza-2′-deoxyguanosine affording the 7- and 8-iodo isomers. The aromatic side chains were introduced by Suzuki–Miyaura cross-coupling or click reaction. Only the 8-phenyl nucleoside shows strong fluorescence in polar aprotic solvents accompanied by solvatochromism. The conformation of the sugar moiety was shifted toward S due to the bulky 8-substituent. Phosphoramidite building blocks and oligonucleotides were synthesized. 8-Substituted 7-deaza-2′-deoxyguanosines destabilize canonical (aps) DNA as well as DNA with parallel strand (ps) orientation. The base pair stability was maintained when the space-occupying substitutes were located at the 7-position. Unexpectedly, the bulky phenyltriazolyl “click” residue is well-accommodated at the 7-position of ps DNA and even led to a stabilization of the parallel double helix. CD spectra indicate that functionalization leads only to local distortion of the double helix while the overall structure of aps and ps DNA is maintained.