Invited Review

Polymer Journal (2017) 49, 279–289; doi:10.1038/pj.2016.120; published online 21 December 2016

Design of photofunctional oligonucleotides by copolymerization of natural nucleobases with base surrogates prepared from acyclic scaffolds

Hiroyuki Asanuma1, Keiji Murayama1, Yukiko Kamiya1 and Hiromu Kashida1,2

  1. 1Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan
  2. 2PRESTO, Japan Science and Technology Agency, Saitama, Japan

Correspondence: Professor H Asanuma, Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan. E-mail: asanuma@nubio.nagoya-u.ac.jp

Received 28 October 2016; Revised 12 November 2016; Accepted 14 November 2016
Advance online publication 21 December 2016

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Abstract

Further development of DNA nanotechnology requires new functional oligonucleotides composed of nucleobases beyond the native four. In this review, we demonstrate new methodology for DNA and RNA functionalization using a base surrogate prepared from d-threoninol (2-amino-1,3-butanediol). Using this nucleobase surrogate, we can introduce functional molecules at any position of the sequence. Our methodology is conceptually similar to the copolymerization of multiple monomers: phosphoramidite monomers corresponding to the base surrogate and natural nucleotides are copolymerized on a solid support to prepare the functional oligonucleotides. Copolymerization allows for stable functional motifs, including wedges, interstrand-wedges, dimers and clusters. By selecting suitable functional molecules and motifs, we can design photofunctional oligonucleotides, such as: (1) photoresponsive DNA that enables reversible formation and dissociation of the duplex by photoirradiation; (2) [2+2] photocycloaddition of stilbene derivatives; (3) orientation-dependent FRET (fluorescence (Förster) resonance energy transfer) systems; (4) sequence-specific fluorescent probe for the detection of DNA and RNA; and (5) functional siRNA for fluorescent labeling of mature RISC (RNA-induced silencing complex).