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 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 Tm in hybridization studies with complementary oligonucleotides.
Awad
Ahmed M
AM
Sektion Chemische Funktionen in Biosystemen, University of Ulm, Ulm, Germany.
Sobkowski
Michal
M
Seliger
Hartmut
H
D000577:Amides / Q000737:chemistry*; D006801:Humans; D009693:Nucleic Acid Hybridization; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D043264:Phosphodiesterase I / Q000737:chemistry; D010756:Phosphoric Acids / Q000737:chemistry*; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000737:chemistry; D044366:Transition Temperature
D000577:Amides; D016376:Oligonucleotides, Antisense; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D015719:Single-Strand Specific DNA and RNA Endonucleases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom