Generation of oligonucleotide conjugates via one-pot diselenide-selenoester ligation-deselenization/alkylation.

ABSTRACT: A breadth of strategies are needed to efficiently modify oligonucleotides with peptides or lipids to capitalize on their therapeutic and diagnostic potential, including the modulation of in vivo chemical stability and for applications in cell-targeting and cell-permeability. The chemical linkages typically used in peptide oligonucleotide conjugates (POCs) have limitations in terms of stability and/or ease of synthesis. Herein, we report an efficient method for POC synthesis using a diselenide-selenoester ligation (DSL)-deselenization strategy that rapidly generates a stable amide linkage between the two biomolecules. This conjugation strategy is underpinned by a novel selenide phosphoramidite building block that can be incorporated into an oligonucleotide by solid-phase synthesis to

SUBMITTER: Liczner C 

PROVIDER: S-EPMC8729807 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature