RNA bulges represent one of the most common motifs in the RNA secondary structure and serve in a variety of biological functions. Compounds stabilizing RNA bulges are important for probing RNA structure and function and for therapy of some diseases. Here, the ability of a series of enantiomeric pairs of optically pure bimetallic metallohelices with different flexible linkers to target various RNA bulges is investigated. The results show that binding affinities of the metallohelices to bulged RNA differ and strongly depend on the size of the bulge and the base composition of the bulge loop. Notably, the shorter, more compact, and less flexible metallohelices bind to RNA bulges most efficiently and selectively. Interestingly, the ability of the metallohelices to bind to RNA bulges correlates with their previously reported antimicrobial activity, which suggests that the selective recognition of bulged regions in RNA by the metallohelices might also contribute to their biological activity.
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