Synthesis of 2'-modified N6-methyladenosine phosphoramidites and their incorporation into siRNA

Bioorg Med Chem Lett. 2023 Jan 9:129126. doi: 10.1016/j.bmcl.2023.129126. Online ahead of print.ABSTRACTA synthesis of 2'-fluoro and 2'-methoxy N6-methyladenosine phosphoramidites and their successful incorporation into oligonucleotides is reported. 2'-fluoro and 2́-methoxy modifications of sugars in siRNAs are known to aid stability and N6-methylation modifies the potency of therapeutic silencing RNAs (siRNA). We demonstrate that a combination of those modifications incorporated into the antisense strand of siRNA leads to efficient knockdown of a target gene in cells. This work broadens the available pool of chemical modifications of therapeutic siRNAs and provides tools for their efficient synthesis.PMID:36632927 | DOI:10.1016/j.bmcl.2023.129126

Source: Bioorganic and Medicinal Chemistry Letters - January 12, 2023 Category: Chemistry Authors: Anna M Rydzik Doris Riether Dirk Gottschling Source Type: research