title: Metal-free catalysts for the hydrolysis of RNA derived from guanidines, 2-aminopyridines, and 2-aminobenzimidazoles.
abstract: 2-aminopyridine and 2-aminobenzimidazole were chosen as structural analogues to substitute guanidinium groups in receptor molecules designed as phosphoryl transfer catalysts. Shifting the pKa of the guanidinium analogues toward 7 was expected to raise catalytic activities in aqueous buffer. Although the pKa's of both heterocycles are similar (6.2 and 7.0), only 2-aminobenzimidazole led to active RNA cleavers. All cleavage assays were run with fluorescently labeled substrates and a DNA sequencer. RNase contaminations would degrade RNA enantioselectively. In contrast, achiral catalysts such as 9b and 10b necessarily induce identical cleavage patterns in RNA and its mirror image. This principle allowed us to safely rule out contamination effects in this study. The most active catalysts, tris(2-aminobenzimidazoles) 9b and 10b, were shown by fluorescence correlation spectroscopy (FCS) to aggregate with oligonucleotides. However, at very low concentrations the compounds are still active in the nonaggregated state. Conjugates of 10b with antisense oligonucleotides or RNA binding peptides, therefore, will be promising candidates as site specific artificial ribonucleases.
authors.affiliation: Institute for Organic Chemistry and Chemical Biology, Goethe-University Frankfurt, Marie-Curie-Str. 11, 60439 Frankfurt am Main, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Scheffer
authors.forename: Andreas
authors.initials: A
authors.lastname: Strick
authors.forename: Verena
authors.initials: V
authors.lastname: Ludwig
authors.forename: Sascha
authors.initials: S
authors.lastname: Peter
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kalden
authors.forename: Michael W
authors.initials: MW
authors.lastname: Göbel
mesh_terms: D000631:Aminopyridines / Q000737:chemistry*; D001483:Base Sequence; D001562:Benzimidazoles / Q000737:chemistry*; D002384:Catalysis; D006146:Guanidines / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000631:Aminopyridines; D001562:Benzimidazoles; D006146:Guanidines; D012313:RNA; C027391:2-aminobenzimidazole; C032439:alpha-aminopyridine