title: Hydrolysis of bulged nucleotides in hybrids formed by RNA and imidazole-derivatized oligo-2'-O-methylribonucleotides.
abstract: In order to enhance the efficacy of small antisense molecules, we examined a series of antisense oligonucleotides derivatized with functional groups designed to enable them to hydrolyze their RNA target. Solid phase synthetic methods were used to prepare imidazole-derivatized antisense oligo-2'-O-methylribonucleotides. Upon binding, these oligonucleotides create internal bulged bases in the target RNA that serve as sites for hydrolysis. We observed that an oligonucleotide derivatized with a side chain containing two imidazole groups was capable of hydrolyzing 58% of its RNA target when incubated with the target for 48 hours at 37°C and physiological pH.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Saleh
authors.forename: Paul S
authors.initials: PS
authors.lastname: Miller
mesh_terms: D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D012313:RNA / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D009711:Nucleotides; D016376:Oligonucleotides, Antisense; D012313:RNA; C029899:imidazole