Enzymatic and Hybridization Properties of Oligonucleotide Analogs Containing Novel Phosphoramidate Internucleotide Linkages

In line with the paradigm, that antisense oligonucleotides should contain minimal structural modifications, in order to minimize the risk of toxicity and antigenicity, we describe here the preparation and the properties of oligonucleotides modified to contain, in addition to phosphodiester bonds, a...

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Bibliographic Details
Published in:Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2004-05, Vol.23 (5), p.777-787
Main Authors: Awad, Ahmed M., Sobkowski, Michal, Seliger, Hartmut
Format: Article
Language:English
Subjects:
Amides - chemistry
Exo- and endonucleolytic stability
Humans
Hybridization
Nucleic Acid Hybridization
Oligoethylene glycol branches
Oligonucleotide analogs
Oligonucleotides, Antisense - chemical synthesis
Oligonucleotides, Antisense - chemistry
Oligonucleotides, Antisense - metabolism
Phosphodiesterase I - chemistry
Phosphoramidate internucleotide
Phosphoric Acids - chemistry
Single-Strand Specific DNA and RNA Endonucleases - chemistry
Transition Temperature
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Summary:In line with the paradigm, that antisense oligonucleotides should contain minimal structural modifications, in order to minimize the risk of toxicity and antigenicity, we describe here the preparation and the properties of oligonucleotides modified to contain, in addition to phosphodiester bonds, a small number of phosphoramidate internucleotide linkages substituted with aminoethoxyethyl groups in order to convey protection against exo- and endonucleases. Prolonged stability was, in fact, found in model experiments with respective enzymes, as well as in studies done in human blood serum. Regardless of number and position of phosphoramidate linkages, the modified oligonucleotides showed only a slight decrease of T m in hybridization studies with complementary oligonucleotides.
ISSN:1525-7770
1532-2335
DOI:10.1081/NCN-120039357