Oligonucleotide compositions and methods thereof
A technology of oligonucleotide and composition, applied in oligonucleotide composition and its field, can solve the problems of limitation, instability, poor cell permeability and distribution, etc.
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[0498] Exemplary substantially racemic preparations of oligonucleotides are obtained by using teraethylthiuram disulfide or (TETD) or 3H-1,2-benzenedithiol-3-one 1 , a preparation of phosphorothioate oligonucleotides of 1-dioxide (BDTD) synthesized from commonly used phosphoramidite oligonucleotides to sulfurize phosphite triesters (a procedure well known in the art). In some embodiments, a substantially racemic preparation of an oligonucleotide provides a substantially racemic oligonucleotide composition (or a chirality-uncontrolled oligonucleotide composition).
[0499] As understood by those of ordinary skill in the art, stereotactic or racemic preparations of oligonucleotides are prepared by non-stereoselective and / or low stereoselective coupling of nucleomonomers, usually without the use of any Chiral auxiliary agent, chiral modifying reagent and / or chiral catalyst. In some embodiments, all or most of the coupling steps are not chirally controlled in substantially racemi...
example
[1133]
[1134] In some embodiments, a modified nucleobase has any of the following structures, optionally substituted:
[1135]
[1136] In some embodiments, the modified nucleobase is fluorescent. Examples of such fluorescent modified nucleobases include phenanthrene, pyrene, stilbene, isoxanthine, isoxantterin, terphenyl, trithiophene, benzotrithiophene, coumarin, lumazine , tethered stilbenes, benzouracils, and naphthouracils, as follows:
[1137]
[1138] In some embodiments, the modified nucleobases are unsubstituted. In some embodiments, modified nucleobases are substituted. In some embodiments, a modified nucleobase is substituted so that it contains, for example, a heteroatom, an alkyl group or a linking moiety attached to a fluorescent moiety, biotin or avidin moiety or other protein or peptide. In some embodiments, a modified nucleobase is a "universal base" that is not a nucleobase in the most classical sense, but functions similarly to a nucleobase. A...
Embodiment approach
[1990] 1. A chiral controlled oligonucleotide composition comprising an oligonucleotide defined by having:
[1991] 1) common base sequence and length;
[1992] 2) common skeletal linkage styles; and
[1993] 3) a common backbone chiral center pattern, said composition being a substantially pure preparation of a single oligonucleotide, wherein a predetermined level of oligonucleotides in said composition have said common base sequence and length, the common skeletal linkage pattern and the common skeletal chiral center pattern.
[1994] 2. A chiral-controlled oligonucleotide composition comprising oligonucleotides of a specific oligonucleotide type, said oligonucleotides being characterized in that:
[1995] 1) common base sequence and length;
[1996] 2) common skeletal linkage styles; and
[1997] 3) Common skeleton chiral center style;
[1998] Said composition is chiral controlled, i.e. said composition is enriched in said particular oligonucleotide type compared to a...
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