Guanidine modification improves functions of natural RNA-targeting alkaloids

One of the important issues for RNA-targeting drugs is to improve their binding properties. Herein, we modified berberine, which interacts with structured RNAs, with the guanidine moiety. Protein expression from target mRNA was efficiently reduced by the modification, suggesting a simple strategy to improve the therapeutic activity. Guanidine modification on berberine improved RNA binding affinity and enhanced suppression of protein expression.