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We report the synthesis of two novel pyrrole-imidazole polyamides with N-terminal guanidinium or tetramethylguanidinium groups and evaluate their antiviral activity against three cancer-causing human papillomavirus strains. Introduction of guanidinium improves antiviral activity when compared to an unsubstituted analog, especially in IC 90 values. These substitutions change DNA-binding preferences, while binding affinity remains unchanged.

Improved antiviral activity of a polyamide against high-risk human papillomavirus via N-terminal guanidinium substitution