PNA monomers fully compatible with standard Fmoc-based solid-phase synthesis of pseudocomplementary PNA

Toru Sugiyama; Genki Hasegawa; Chie Niikura; Keiko Kuwata; Yasutada Imamura; Yosuke Demizu; Masaaki Kurihara; Atsushi Kittaka

doi:10.1016/j.bmcl.2017.06.015

PNA monomers fully compatible with standard Fmoc-based solid-phase synthesis of pseudocomplementary PNA

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3337-3341. doi: 10.1016/j.bmcl.2017.06.015. Epub 2017 Jun 3.

Authors

Toru Sugiyama¹, Genki Hasegawa², Chie Niikura², Keiko Kuwata³, Yasutada Imamura⁴, Yosuke Demizu⁵, Masaaki Kurihara⁶, Atsushi Kittaka⁷

Affiliations

¹ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan. Electronic address: tsugiyama@pharm.teikyo-u.ac.jp.
² Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan.
³ Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
⁴ Faculty of Engineering, Kogakuin University, 2665-1 Nakano, Hachioji, Tokyo 192-0015, Japan.
⁵ Division of Organic Chemistry, National Institute of Health Sciences, Ministry of Health and Welfare, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
⁶ School of Pharmacy, International University of Health and Welfare, 2600-1, Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
⁷ Faculty of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan. Electronic address: akittaka@pharm.teikyo-u.ac.jp.

PMID: 28610975
DOI: 10.1016/j.bmcl.2017.06.015

Abstract

Here we report the synthesis of new PNA monomers for pseudocomplementary PNA (pcPNA) that are fully compatible with standard Fmoc chemistry. The thiocarbonyl group of the 2-thiouracil (sU) monomer was protected with the 4-methoxy-2-methybenzyl group (MMPM), while the exocyclic amino groups of diaminopurine (D) were protected with Boc groups. The newly synthesized monomers were incorporated into a 10-mer PNA oligomer using standard Fmoc chemistry for solid-phase synthesis. Oligomerization proceeded smoothly and the HPLC and MALDI-TOF MS analyses indicated that there was no remaining MMPM on the sU nucleobase. The new PNA monomers reported here would facilitate a wide range of applications, such as antigene PNAs and DNA nanotechnologies.

Keywords: Antigene; Peptide nucleic acid; Pseudocomplementary; Strand invasion.

Publication types

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

MeSH terms

Molecular Structure
Peptide Nucleic Acids / chemical synthesis*
Peptide Nucleic Acids / chemistry
Solid-Phase Synthesis Techniques*

Substances

Peptide Nucleic Acids