A facile and general tandem oligonucleotide synthesis methodology for DNA and RNA

Chembiochem. 2024 Jan 5:e202300870. doi: 10.1002/cbic.202300870. Online ahead of print.ABSTRACTTandem oligonucleotide synthesis (TOS) is an attractive strategy to increase automated oligonucleotide synthesis efficiency. TOS is accomplished via the introduction of an immolative linker within a single sequence composed of multiple oligonucleotide fragments. Here, we report the use of a commercially available building block, typically utilized for the chemical phosphorylation of DNA/RNA oligomers, to perform TOS. We show that the 2,2'-sulfonyldiethylene linker is efficiently self-immolated during the standard deprotection of DNA and RNA and presents itself as a generalizable methodology for nucleic acid TOS. Furthermore, we show the utility of this methodology by assembling a model siRNA construct, and showcase a template-directed ligation pathway to incorporate phosphoramidate or pyrophosphate linkages within DNA oligomers.PMID:38179859 | DOI:10.1002/cbic.202300870

Source: Chembiochem - January 5, 2024 Category: Biochemistry Authors: Jagandeep S Saraya Derek O'Flaherty Source Type: research