Synthesis and properties of PNA containing a dicationic nucleobase based on N4-benzoylated cytosine

Shun-Suke Moriya; Kaoru Funaki; Yosuke Demizu; Masaaki Kurihara; Atsushi Kittaka; Toru Sugiyama

doi:10.1016/j.bmcl.2023.129287

Synthesis and properties of PNA containing a dicationic nucleobase based on N⁴-benzoylated cytosine

Bioorg Med Chem Lett. 2023 May 15:88:129287. doi: 10.1016/j.bmcl.2023.129287. Epub 2023 Apr 22.

Authors

Shun-Suke Moriya¹, Kaoru Funaki¹, Yosuke Demizu², Masaaki Kurihara³, Atsushi Kittaka¹, Toru Sugiyama⁴

Affiliations

¹ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan.
² Division of Organic Chemistry, National Institute of Health Sciences, Ministry of Health and Welfare, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.
³ Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Yokohama, Kanagawa 244-0806, Japan.
⁴ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan. Electronic address: tsugiyama@pharm.teikyo-u.ac.jp.

PMID: 37094725
DOI: 10.1016/j.bmcl.2023.129287

Abstract

We report the synthesis of a peptide nucleic acid (PNA) monomer containing N⁴-bis(aminomethyl)benzoylated cytosine (^BzC²⁺ base). The ^BzC²⁺ monomer was incorporated into PNA oligomers using Fmoc-based solid-phase synthesis. The ^BzC²⁺ base in PNA had two positive charges and exhibited greater affinity for DNA G base than the natural C base. The ^BzC²⁺ base stabilized PNA-DNA heteroduplexes through electrostatic attractions, even in high salt conditions. The two positive charges on the ^BzC²⁺ residue did not compromise the sequence specificity of PNA oligomers. These insights will aid the future design of cationic nucleobases.

Keywords: Antigene; Peptide nucleic acid; Positive charge; Strand invasion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytosine
DNA / chemistry
Peptide Nucleic Acids* / chemistry

Substances

Peptide Nucleic Acids
Cytosine
DNA