申请人:Manoharan Muthiah
公开号:US20060287260A1
公开(公告)日:2006-12-21
One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.
本发明的一个方面涉及在3'-位置用磷酰胺基团取代的核糖核苷。在某些实施例中,磷酰胺基团是烷基磷酰胺基团。本发明的另一个方面涉及包含至少一个非磷酸酯连接的双链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼基、酰胺和碳酸酯连接。在某些实施例中,非磷酸酯连接是磷酸酯连接。在某些实施例中,非磷酸酯连接仅出现在一条链中。在某些实施例中,非磷酸酯连接出现在两条链中。在某些实施例中,配体结合到包含双链寡核苷酸的寡核苷酸链中的一条链上。在某些实施例中,配体结合到包含双链寡核苷酸的寡核苷酸链中的两条链上。在某些实施例中,寡核苷酸链包含至少一个修饰的糖基团。本发明的另一个方面涉及包含至少一个非磷酸酯连接的单链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼基、酰胺和碳酸酯连接。在某些实施例中,非磷酸酯连接是磷酸酯连接。在某些实施例中,配体结合到寡核苷酸链上。在某些实施例中,寡核苷酸包含至少一个修饰的糖基团。