Activation of human RNase L by 2'- and 5'-O-methylphosphonate-modified oligoadenylates. 2012

Ondřej Páv, and Natalya Panova, and Jan Snášel, and Eva Zborníková, and Ivan Rosenberg
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 166 10 Prague 6, Czech Republic.

To determine the influence of internucleotide linkage and sugar ring conformation, and the role of 5'-terminal phosphate, on the activation of human RNase L, a series of 2'- and 5'-O-methylphosphonate-modified tetramers were synthesized from appropriate monomeric units and evaluated for their ability to activate human RNase L. Tetramers pAAAp(c)X modified by ribo, arabino or xylo 5'-phosphonate unit p(c)X activated RNase L with efficiency comparable to that of natural activator. Moreover, incorporation of phosphonate linkages ensured the stability against cleavage by nucleases. The substitution of 5'-terminal phosphate for 5'-terminal phosphonate in tetramer p(c)XAAA afforded tetramers with excellent activation efficiency and with complete stability against cleavage by phosphomonoesterases.

UI MeSH Term Description Entries
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D009843 Oligoribonucleotides A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
D002474 Cell-Free System A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166) Cellfree System,Cell Free System,Cell-Free Systems,Cellfree Systems,System, Cell-Free,System, Cellfree,Systems, Cell-Free,Systems, Cellfree
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D004722 Endoribonucleases A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-. Endoribonuclease
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000227 Adenine Nucleotides Adenine Nucleotide,Adenosine Phosphate,Adenosine Phosphates,Nucleotide, Adenine,Nucleotides, Adenine,Phosphate, Adenosine,Phosphates, Adenosine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs

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