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

Kwang Suk Lim; Daniel Y Lee; Gabriel M Valencia; David A Bull; Young-Wook Won

doi:10.1021/acsmacrolett.6b00865

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

ACS Macro Lett. 2017 Feb 21;6(2):98-102. doi: 10.1021/acsmacrolett.6b00865. Epub 2017 Jan 17.

Authors

Kwang Suk Lim¹, Daniel Y Lee^{1

2}, Gabriel M Valencia¹, David A Bull^{1

2}, Young-Wook Won^{1

2}

Affiliations

¹ Division of Cardio-Thoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah 84132, United States.
² Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.

PMID: 35632899
DOI: 10.1021/acsmacrolett.6b00865

Abstract

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.