Artificial ribonucleases

Abstract

Mimicking the action of enzymes by simpler and more robust man-made catalysts has long inspired bioorganic chemists. During the past decade, mimics for RNA-cleaving enzymes, ribonucleases, or, more precisely, mimics of ribozymes that cleave RNA in sequence-selective rather than base-selective manner, have received special attention. These artificial ribonucleases are typically oligonucleotides (or their structural analogs) that bear a catalytically active conjugate group and catalyze sequence-selective hydrolysis of RNA phosphodiester bonds.

2'-O-Methyloligoribonucleotide based artificial nucleases (2’-O-MeOBAN’s) cleaving a model of the leukemia related M-BCR/ABL m-RNA

“…Cleavage rates for OBANs in general display only a modest distribution, even though different catalytic groups have been used. 1,11 For real use in disease therapeutics the overall rate of RNA cleavage, as catalyzed by any so far developed OBANs, is likely to be insufficient for efficient suppression of gene expression. Clearly something more is needed to take a leap forward in the development of the efficiency of OBANs.…”

“…Metal complexes linked to oligonucleotides can be reasonable catalysts for the cleavage of ribonucleic acids. 1 and several studies demonstrate the potential for targeting biologically relevant RNAs with artificial ribonucleases. [2][3][4] All systems developed so far clearly still have some distance to go in order to achieve rates efficient enough for use in a therapeutic setting.…”

Synthesis and characterization of some water soluble Zn(ii) complexes with (E)-N-(pyridin-2-ylmethylene)arylamines that regulate tumour cell death by interacting with DNA

“…Hence, efficient Zn(II)-based hydrolytic cleavage agents are good candidates for biomedical applications. 44,45 In view of the conspicuous importance of the unsymmetrical iminopyridyl systems as metal chelators in catalysis and in biology, we now report the synthesis and full characterization of water soluble zinc(II) compounds of (E) Consequently, the dichlorozinc compounds 1, 3-5 and 8 were investigated in vitro on HeLa tumour cell lines in order to assess the influence of various substituents and of the metal coordination number on the biological activities.…”

Mechanism of the toxicity of the artificial ribonucleases for the different human cancer cell lines

“…В настоящее время ведутся разработки противоопухолевого препарата на основе онконазы. 230 * -адресат для переписки В последнее время большой интерес вызывают соединения, способные эффективно расщеплять РНК -искусственные РНКазы (аРНКазы) [5]. Эти соединения, подобно природным ферментам, катализируют реакцию трансэтерификации в физиологических условиях и необратимо разрушают РНК.…”

“…Химические рибонуклеазы -это низкомолекулярные соединения различной природы, способные катализировать расщепление РНК в мягких условиях [5]. Ранее было показано, что расщепление РНК в физиологических условиях (рН 7,0, 37°С) происходит эффективно в присутствии целого ряда соединений, имитирующих активные центры природных РНКаз [7,13,14].…”