We have developed 2'-O-methyloligoribonucleotide and peptide nucleic acid (PNA) based artificial ribonucleases (OBAN's), which in presence of zinc or copper ions cleave a potential therapy target in leukemia, an M-BCR/ABL mRNA model. The OBAN's give turnover of substrate and are thus real enzymes. A copper ion based system even gives single site cleavage in the RNA-substrate.
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Development of 2'-o-methyloligoribonucleotide and peptide nucleic acid based artificial ribonucleases.
Nucleic Acids Symp Ser (Oxf)
April 2008
Department of Biosciences & Nutrition, Novum, Karolinska Institutet, S-14157 Huddinge, Sweden.
We have developed 2'-O-methyloligoribonucleotide and peptide nucleic acid (PNA) based artificial ribonucleases (OBAN's), which in presence of zinc or copper ions cleave a potential therapy target in leukemia, an M-BCR/ABL mRNA model. The OBAN's give turnover of substrate and are thus real enzymes. A copper ion based system even gives single site cleavage in the RNA-substrate.
View Article and Find Full Text PDFPreparation of azacrown-functionalized 2'-O-methyl oligoribonucleotides, potential artificial RNases.
Bioconjug Chem
March 2004
Department of Chemistry, University of Turku, FIN-20014 Turku, Finland.
An improved synthesis for 3-(3-aminopropyl)- and 3-(3-mercaptopropyl)-1,5,9-triazacyclododecane has been developed and alternative methods for their conjugation to oligonucleotides have been described. Accordingly, the 3-aminopropyl azacrown and its N-(3-aminopropanoyl)-3-aminopropyl analogue have been tethered to the 3'-terminus of a 2'-O-methyloligoribonucleotide by aminolytic cleavage of the thioester linker utilized for the chain assembly. Studies on a monomeric model compound verify that the reaction proceeds solely by the attack of the primary amino group.
View Article and Find Full Text PDFSynthesis of peptide-oligonucleotide conjugates with single and multiple peptides attached to 2'-aldehydes through thiazolidine, oxime, and hydrazine linkages.
Bioconjug Chem
August 2003
Chemistry Department and A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University, Moscow, 119899, Russia.
2'-Deoxyoligonucleotides and 2'-O-methyloligoribonucleotides carrying one or more 2'-aldehyde groups were synthesized and coupled to peptides containing an N-terminal cysteine, aminooxy, or hydrazide group to give peptide-oligonucleotide conjugates incorporating single or multiple peptides in good yield. The facile conjugation method allows specific coupling in aqueous solution of unprotected oligonucleotides containing aldehyde groups to unprotected N-terminally modified peptides and other small molecules. A 12-mer 2'-O-methyloligoribonucleotide complementary to the HIV-1 TAR RNA stem-loop and containing two conjugated copies of an 8-mer model laminin peptide was hardly affected in TAR RNA binding and showed a similar level of inhibition of HIV-1 Tat-dependent in vitro transcription compared to the unconjugated 2'-O-methyloligoribonucleotide.
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