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The well-characterized interaction between the MS2 coat protein and its cognate RNA hairpin was used to evaluate changes in affinity as a result of phosphorodithioate (PS2) replacing phosphate by biolayer interferometry (BLI). A structure-based analysis of the data provides insights into the origins of the enhanced affinity of RNA–protein interactions triggered by the PS2 moiety.

Graphical abstract: Origins of the enhanced affinity of RNA–protein interactions triggered by RNA phosphorodithioate backbone modification

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