Abstract
2-Methyladenosine-substituted analogues of 2-5A, p5'A2'p5'A2'p5'(me2A), p5'(me2A)2'p5'A2'p5'A, and p5'(me2A) 2'p5'(me2A)2'pS'(me2A), were prepared via a modification of a lead ion-catalyzed ligation reaction. These 5'-monophosphates were subsequently converted into the corresponding 5'-triphosphates. Both binding and activation of human recombinant RNase L by various 2-methyladenosine-substituted 2-5A analogues were examined. Among the 2-5A analogues, p5'A2'p5'A2'p5'(me2A) showed the strongest binding affinity and was as effective as 2-5A itself as an activator of RNase L. The CD spectra of both p5'(me2A)2'p5'A2'p5'A and p5'A2'p5'A2'p5'(me2A) were superimposable on that of p5'A2'p5'A2'p5'A, indicative of an anti orientation about the base-glycoside bonds as in naturally occurring 2-5A.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / chemistry
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Adenosine / pharmacology
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Adenosine Monophosphate / analogs & derivatives
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Adenosine Monophosphate / chemistry*
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Adenosine Monophosphate / pharmacology*
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Binding Sites
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Catalysis / drug effects
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Circular Dichroism
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Endoribonucleases / drug effects*
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Endoribonucleases / metabolism
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Humans
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Magnetic Resonance Spectroscopy
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Nucleic Acid Conformation
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Oligoribonucleotides / chemistry*
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Oligoribonucleotides / pharmacology*
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Protein Binding
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Oligoribonucleotides
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Recombinant Proteins
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2-methyladenosine
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Adenosine Monophosphate
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Endoribonucleases
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2-5A-dependent ribonuclease
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Adenosine