Dicerna Pharmaceuticals, Inc.
4'-phosphate analogs and oligonucleotides comprising the same

Abstract:

Disclosed herein are oligonucleotides, such as nucleic acid inhibitor molecules, having a 4'-phosphate analog and methods of using the same, for example, to modulate the expression of a target gene in a cell. The oligonucleotide of the disclosure comprises a 5'-terminal nucleotide represented by Formula III: ##STR00001## wherein R.sup.a, R.sup.b, B, X.sub.2 and Y are as defined in the specification. The phosphate analogs are bound to the 4'-carbon of the sugar moiety (e.g., a ribose or deoxyribose or analog thereof) of the 5'-terminal nucleotide of an oligonucleotide. Typically, the phosphate analog is an oxymethylphosphonate, where the oxygen atom of the oxymethyl group is bound to the 4'-carbon of the sugar moiety or analog thereof. An illustrative 5'-terminal nucleotide of an oligonucleotide of the disclosure may have the following chemical structure: ##STR00002##