Solid-phase synthesis of the self-complementary hexamer d(c7GpCpc7GpCpc7GpC) via the O-3'-phosphoramidite of 7-deaza-2'-deoxyguanosine.
The synthesis of the O-3'-phosphoramidite of a suitably protected 7-deaza-2'-deoxyguanosine (c7G) which is an isostere of 2'-deoxyguanosine is described. The phosphoramidite of the modified nucleoside was used in the synthesis of the self-complementary hexamer d(c7GpCpc7GpCpc7GpC) on functionalized silica gel in a mini-reactor. As expected from the parent hexamer d(GpCpGpCpGpC) the isosteric d(c7GpCpc7GpCpc7GpC) exhibits a rigid secondary structure (22% hypochromicity at 280 nm) and forms a duplex in 1 M aqueous sodium chloride solution. Due to the altered pi-electron system of the pyrrolo[2,3-d]pyrimidine nucleobase, which affects base stacking and hydrogen bonding, the Tm of the modified duplex is decreased by 10 degrees C compared to that of the parent purine hexamer. Moreover, it is expected that the incorporation of c7G influences the pitch of the helix.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives*; D006150:Guanine Nucleotides / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D009841:Oligonucleotides / Q000138:chemical synthesis*
D006150:Guanine Nucleotides; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; C045550:7-deaza-2'-deoxyguanosine; D003849:Deoxyguanosine