N-terminal Cationic Modification of Linear Pyrrole-Imidazole Polyamide Improves Its Binding to DNA

Pyrrole-imidazole polyamides (PIPs) bind to double-stranded DNA (dsDNA) with varied sequence selectivity. We synthesized linear PIPs that can bind to narrow minor grooves of polypurine/polypyrimidine sequences and target long recognition sequences but have lower molecular weights than commonly used hairpin PIPs. We modified the N-terminus of linear PIPs using several groups, including beta-alanine extension and acetyl capping. Melting curve analysis of dsDNA demonstrated that cationic modifications improved the binding affinity of the PIPs to the targeted dsDNA. In addition, circular dichroism assays revealed the characteristic spectra depending on the binding stoichiometry of the N-cationic linear PIP and dsDNA (1 : 1, monomeric; 2 : 1, dimeric). Surface plasmon resonance assays confirmed the high binding affinities of linear PIPs. These findings may aid in the design of effective linear PIPs.

Automated summary

In this study, we synthesized linear pyrrole-imidazole polyamides (PIPs) that can selectively bind to DNA. These linear PIPs have lower molecular weights compared to commonly used hairpin PIPs. The binding affinity of the PIPs to DNA was improved by modifying the N-terminus of the linear PIPs. These findings provide insights for the design of effective linear PIPs.