Hybridization Properties of RNA Containing 8-Methoxyguanosine and 8-Benzyloxyguanosine.
Modified nucleobase analogues can serve as powerful tools for changing physicochemical and biological properties of DNA or RNA. Guanosine derivatives containing bulky substituents at 8 position are known to adopt syn conformation of N-glycoside bond. On the contrary, in RNA the anti conformation is predominant in Watson-Crick base pairing. In this paper two 8-substituted guanosine derivatives, 8-methoxyguanosine and 8-benzyloxyguanosine, were synthesized and incorporated into oligoribonucleotides to investigate their influence on the thermodynamic stability of RNA duplexes. The methoxy and benzyloxy substituents are electron-donating groups, decreasing the rate of depurination in the monomers, as confirmed by N-glycoside bond stability assessments. Thermodynamic stability studies indicated that substitution of guanosine by 8-methoxy- or 8-benzyloxyguanosine significantly decreased the thermodynamic stability of RNA duplexes. Moreover, the presence of 8-substituted guanosine derivatives decreased mismatch discrimination. Circular dichroism spectra of modified RNA duplexes exhibited patterns typical for A-RNA geometry.
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.
Daniel Sylwester
DS
Baranowski
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.
Weronika
W
Kotkowiak
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.
Ryszard
R
Kierzek
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.
Anna
A
Pasternak
D020029:Base Pairing; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D013816:Thermodynamics
D009692:Nucleic Acid Heteroduplexes; D009841:Oligonucleotides; D006151:Guanosine; D012313:RNA; C046214:8-methoxyguanosine; D004247:DNA