2025/02/20 by Maria Nerantzaki, Claire Husser, Isaure Sergent +3 · 1 voice
Chemistry · #Synthetic Organic Chemistry Methods
paper · doi:10.1021/acs.bioconjchem.4c00540
openalex publication_date 2025/02/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
A reliable method for the efficient chemical synthesis and poly(ethylene glycol) PEG-like modification of fluorogenic RNA aptamers is reported. The 43-mer version of Mango-II RNA (MangoII-v1), which binds tightly and specifically to the green fluorophore TO1-Biotin (TO1-B), was synthesized by automated phosphoramidite chemistry using 2′- O -[(triisopropylsilyl)oxy]methyl] (2′- O -TOM)-protected ribonucleosides. Solid-phase phosphoramidite chemistry was also used as a single tool to prepare MangoII-v1 modified with a PEG-like oligophosphate synthetic segment (MangoII-v1- P ). After cleavage from the resin, deprotection, and purification, the capacity to activate the fluorescence of TO1-B and the degradation behavior of the chemically synthesized RNAs MangoII-v1 and MangoII-v1- P, were deeply investigated in comparison with those of the enzymatically synthesized 48 nucleotides long RNA MangoII. Interestingly, the chemically synthesized MangoII-v1 RNA aptamer demonstrated great activity toward its target, compared to the enzymatically synthesized analogue. Moreover, it was found to be highly stable, retaining its structural integrity and bioactivity, even after seven days of incubation in 20% fetal bovine serum. MangoII-v1- P also showed a high affinity for TO1-B and excellent degradation resistance.