title: Synthesis and cleavage experiments of oligonucleotide conjugates with a diimidazole-derived catalytic center.
abstract: Ribonuclease mimics based on diimidazole derived constructs in combination with or without additional amino groups have been synthesized and conjugated to oligonucleotides. The imidazole moiety was used either unprotected, protected with a monomethoxytrityl group or a tert-butyloxy carbonyl group. Acylation reactions were carried out using the 3-acyl-1,3-thiazolidine-2-thione activation strategy. The peptides were coupled to the oligonucleotides with a mixture of PyBOP, DIEA an HOBt in DMF on solid support. The conjugates were purified by RP-HPLC and identified using negative ion mode mass spectrometry. Unfortunately, no cleavage of a linear RNA target under physiological conditions could be observed.
authors.affiliation: Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Birgit
authors.initials: B
authors.lastname: Verbeure
authors.forename: Carl Jeff
authors.initials: CJ
authors.lastname: Lacey
authors.forename: Mattheus
authors.initials: M
authors.lastname: Froeyen
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D013696:Temperature
chemical_list: D007093:Imidazoles; D009841:Oligonucleotides; D012313:RNA; D012259:Ribonuclease, Pancreatic