The synthesis of solid supports carrying base labile linkers to generate 3'-phosphate oligonucleotides

Oligonucleotides carrying 3'-terminal phosphates and conjugates are important tools in molecular biology and diagnostic purposes. We described the preparation of solid supports carrying the base labile linker 4-((2-hydroxyethyl)sulfonyl)benzamide for the solid-phase synthesis of 3'-phosphorylated oligonucleotides. These supports are fully compatible with the phosphoramidite chemistry yielding the desired 3'-phosphate oligonucleotides in excellent yields. The use of mild deprotection conditions allows the generation of partially protected DNA fragments.This work was financially supported by the Spanish Ministerio de Ciencia e Innovación (MICINN) (Projects PID2020-118145RB-I00, CPP2021-008792 and PID2022-137893OB-I00), and NRF-South Africa. This research was also supported by CIBER - Consorcio Centro de Investigación Biomédica en Red (CB06/01/0019), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and the European Regional Development Fund (ERDF). The oligonucleotide synthesis was performed by the ICTS ‘‘NANBIOSIS” and specifically by the oligonucleotide synthesis platform (OSP) U29 at IQAC-CSIC (https://www.nanbiosis.es/portfolio/u29-oligonucleotide-synthesis-platform-osp/). We thank Dr. Ramon Güimil-Garcia (BioNTech RNA Pharmaceuticals) for his encouragement and discussions.Peer reviewe