Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom

• Main Authors: Manoharan, Muthiah, Cook, Phillip Dan, Prakash, Thazha P, Kawasaki, Andrew M
• Format: Patent
• Language: English
• Published: 28.10.2003

This invention is directed to aminooxy-modified nucleosides and oligonucleotides, to oligonucleotides that elicit RNase H for cleavage in a complementary nucleic acid strand, and to oligonucleotides wherein at least some of the nucleotides are functionalized to be nuclease resistant, at least some of the nucleotides of the oligonucleotide including a substituent that potentiates hybridization of the oligonucleotide to a complementary strand of nucleic acid, and at least some of the nucleotides of the oligonucleotide include 2′-deoxy-erythro-pentofuranosyl sugar moiety. The inclusion of one or more aminooxy moieties in such oligonucleotide provides, inter alia, for improved binding of the oligonucleotides to a complementary strand. The oligonucleotides and macromolecules are useful for therapeutics, diagnostics and as research reagents. Nucleosidic monomers and oligomeric compounds prepared therefrom are provided which have increased nuclease resistance, substituent groups (such as 2′-aminooxy groups) for increasing binding affinity to complementary strand, and regions of 2′-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.