Site-specific cleavage of RNA by a metal-free artificial nuclease attached to antisense oligonucleotides.
RNA cleaving tris(2-aminobenzimidazoles) have been attached to DNA oligonucleotides via disulfide or amide bonds. The resulting conjugates are effective organocatalytic nucleases showing substrate and site selectivity as well as saturation kinetics. The benzimidazole conjugates also degrade enantiomeric RNA. This observation rules out contamination effects as an alternative explanation of RNA degradation. The pH dependency shows that the catalyst is most active in the deprotonated state. Typical half-lifes of RNA substrates are in the range of 12-17 h. Thus, conjugates of tris(2-aminobenzimidazoles) can compete with the majority of metal-dependent artificial nucleases.
Gnaccarini
Claudio
C
Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Marie-Curie-Str. 11, D-60439 Frankfurt am Main, Germany.
Peter
Sascha
S
Scheffer
Ute
U
Vonhoff
Stefan
S
Klussmann
Sven
S
Göbel
Michael W
MW
D000577:Amides / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001562:Benzimidazoles / Q000737:chemistry*; D002384:Catalysis; D004247:DNA / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008670:Metals / Q000737:chemistry*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
D000577:Amides; D001562:Benzimidazoles; D004220:Disulfides; D008670:Metals; D016376:Oligonucleotides, Antisense; D012313:RNA; D004247:DNA; C027391:2-aminobenzimidazole