Characterization of Non-Specific Electrostatic Interactions of Cationic Peptides with DNA Origami and Their Functional Consequences.

ABSTRACT: The functionalization of DNA origami with peptides is a powerful strategy for creating nanodevices for therapeutic and diagnostic applications. A critical but often overlooked challenge is the non-specific electrostatic binding of cationic peptides to the anionic DNA nanostructure, which leads to uncontrolled stoichiometry and undermines functional predictability. Here, the study systematically characterizes this issue and demonstrates a practical purification strategy to mitigate it. It is quantitatively shown that cationic peptides associate with DNA origami in vast excess of their intended binding sites, a phenomenon not observed with anionic control peptides. This non-specific binding is confirmed to be electrostatic and is effectively screened by high salt. To address this, a charge-d

SUBMITTER: Kang SH 

PROVIDER: S-EPMC12790360 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature