title: The chemical stability of abasic RNA compared to abasic DNA.
abstract: We describe the synthesis of an abasic RNA phosphoramidite carrying a photocleavable 1-(2-nitrophenyl)ethyl (NPE) group at the anomeric center and a triisopropylsilyloxymethyl (TOM) group as 2'-O-protecting group together with the analogous DNA and the 2'-OMe RNA abasic building blocks. These units were incorporated into RNA-, 2'-OMe-RNA- and DNA for the purpose of studying their chemical stabilities towards backbone cleavage in a comparative way. Stability measurements were performed under basic conditions (0.1 M NaOH) and in the presence of aniline (pH 4.6) at 37 degrees C. The kinetics and mechanisms of strand cleavage were followed by High pressure liquid chromotography and ESI-MS. Under basic conditions, strand cleavage at abasic RNA sites can occur via beta,delta-elimination and 2',3'-cyclophosphate formation. We found that beta,delta-elimination was 154-fold slower compared to the same mechanism in abasic DNA. Overall strand cleavage of abasic RNA (including cyclophosphate formation) was still 16.8 times slower compared to abasic DNA. In the presence of aniline at pH 4.6, where only beta,delta-elimination contributes to strand cleavage, a 15-fold reduced cleavage rate at the RNA abasic site was observed. Thus abasic RNA is significantly more stable than abasic DNA. The higher stability of abasic RNA is discussed in the context of its potential biological role.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors.forename: Pascal A
authors.initials: PA
authors.lastname: Küpfer
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Leumann
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009843:Oligoribonucleotides / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D012313:RNA / Q000737:chemistry*
chemical_list: D000814:Aniline Compounds; D009841:Oligonucleotides; D009843:Oligoribonucleotides; D009943:Organophosphorus Compounds; D010710:Phosphates; C434331:phosphoramidite; D012313:RNA; D004247:DNA; C023650:aniline