Synthesis and characterization of PNA oligomers containing preQ1 as a positively charged guanine analogue

Shun-Suke Moriya; Hatsune Shibasaki; Misaki Kohara; Keiko Kuwata; Yasutada Imamura; Yosuke Demizu; Masaaki Kurihara; Atsushi Kittaka; Toru Sugiyama

doi:10.1016/j.bmcl.2021.127850

Synthesis and characterization of PNA oligomers containing preQ₁ as a positively charged guanine analogue

Bioorg Med Chem Lett. 2021 May 1:39:127850. doi: 10.1016/j.bmcl.2021.127850. Epub 2021 Mar 2.

Authors

Shun-Suke Moriya¹, Hatsune Shibasaki¹, Misaki Kohara¹, Keiko Kuwata², Yasutada Imamura³, Yosuke Demizu⁴, Masaaki Kurihara⁵, Atsushi Kittaka⁶, Toru Sugiyama⁷

Affiliations

¹ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan.
² Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
³ Faculty of Engineering, Kogakuin University, 2665-1 Nakano, Hachioji, Tokyo 192-0015, Japan.
⁴ 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.
⁵ School of Pharmacy, International University of Health and Welfare, 2600-1, Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
⁶ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan. Electronic address: akittaka@pharm.teikyo-u.ac.jp.
⁷ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan. Electronic address: tsugiyama@pharm.teikyo-u.ac.jp.

PMID: 33662538
DOI: 10.1016/j.bmcl.2021.127850

Abstract

We report the synthesis of a peptide nucleic acid (PNA) monomer containing preQ₁, a positively charged guanine analogue. The new monomer was incorporated into PNA oligomers using standard Fmoc-chemistry-based solid-phase synthesis. The preQ₁ unit-containing PNA oligomers exhibited improved affinity for their complementary DNA through electrostatic attraction, and their sequence specificity was not compromised. It could be beneficial to incorporate preQ₁ into PNA oligomers instead of guanine when creating antisense/antigene agents or research tools.

Keywords: Antigene; Peptide nucleic acid; Positive charge; Strand invasion; preQ(1).

Publication types

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

MeSH terms

Molecular Structure
Peptide Nucleic Acids / chemical synthesis*
Peptide Nucleic Acids / chemistry
Pyrimidinones / chemistry*
Pyrroles / chemistry*

Substances

7-(aminomethyl)-7-deazaguanine
Peptide Nucleic Acids
Pyrimidinones
Pyrroles