Direct Incorporation of Functional Peptides into M-DNA through Ligand-to-Metal Charge Transfer

Conventional nonviral gene delivery methods suffer from the toxicity of the cationic nature of polymeric carriers. There is a significant need for a new method of gene delivery that overcomes the limitations and allows targeted gene delivery. In this study, we have developed a new method to incorporate functional peptides into DNA without the need for chemical conjugations by utilizing a ligand-to-metal charge transfer (LMCT) transition, which occurs between divalent metal ions and the sulfhydryl group in cysteine. To apply the LMCT transition to the incorporation of cysteine-containing targeting peptides into DNA, divalent metal ions must be first introduced to DNA. Zn²⁺ ions spontaneously intercalate into the DNA base pairs in the pH range of 7.0-8.5, resulting in the conversion of normal B-DNA to metal-bound DNA (M-DNA). We found that the Zn²⁺ ions present in M-DNA could interact with the sulfhydryl groups in cysteines of targeting peptides through the LMCT transition, and the M-DNA/peptide complex could specifically transfect the target cells.