Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond.

ABSTRACT: One of the key problems in the design of therapeutic and diagnostic oligonucleotides is the attachment of small-molecule ligands for targeted deliveries in such a manner that provides the controlled release of the oligonucleotide at a certain moment. Here, we propose a novel, convenient approach for attaching ligands to the 5'-end of the oligonucleotide via biodegradable, acid-labile phosphoramide linkage. The method includes the activation of the 5'-terminal phosphate of the fully protected, support-bound oligonucleotide, followed by interaction with a ligand bearing the primary amino group. This technique is simple to perform, allows for forcing the reaction to completion by adding excess soluble reactant, eliminates the problem of the limited solubility of reagents, and affords the poss

SUBMITTER: Kropacheva NO 

PROVIDER: S-EPMC9961013 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature