SDS 5'-POM-Vinyl phosphonate 2'-O-Methyl Uridine 3'-CE phosphoramidite

POM-protected phosphoramidite for incorporation of a 5′-(E)-vinylphosphonate (VP) moiety into an oligonucleotide. (E)‑Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5′-end of the antisense strand, enhances the in vivo potency of siRNA.

The standard dU nucleobase is chemically ligated with a hydrolytically impervious 5’ vinyl phosphonate (VP), an effective bioisostere of the natural 5′-monophosphate in small interfering RNAs (siRNAs). VPs are shown to enhance RNA-induced silencing complex (RISC) recognition and thus avoid the use of metabolically unstable 5’ phosphates. There is some evidence to suggest enhancement of exonuclease stability. Of particular use where a sequence is incompatible with cellular kinases and thus cannot be 5’ phosphorylated in-vitro. ^(1,2)

Two options are available, either OMe or POM protection. 5'-[O,O-bis(pivaloyloxymethyl)] (POM) protection allows clean and rapid one-step deprotection with addition of 3% (v/v) diethylamine to the standard aqueous ammonia deprotection solution, minimizing side reactions and impurities.

References:

1.   ChemBioChem 2016, 17, 985-989 (DOI: 10.1002/cbic.201600130).

2.   J. Med. Chem. 2018, 61, 734-744 (DOI: 10.1021/acs.jmedchem.7b01147).