In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization.

Greta Linden,Olalla Vázquez,Lei Zhang

doi:10.3762/bjoc.15.243

Abstract

Photoswitchable oligonucleotides can determine specific biological outcomes by light-induced conformational changes. In particular, artificial probes activated by visible-light irradiation are highly desired in biological applications. Here, we report two novel types of visible-light photoswitchable peptide nucleic acids (PNAs) based on the molecular transducers: hemithioindigo and tetra-ortho-fluoroazobenzene. Our study reveals that the tetra-ortho-fluoroazobenzene–PNA conjugates have promising properties (fast reversible isomerization, exceptional thermal stability, high isomer conversions and sensitivity to visible-light irradiation) as reversible modulators to control oligonucleotide hybridization in biological contexts. Furthermore, we verified that this switchable modification delivers a slightly different hybridization behavior in the PNA. Thus, both melting experiments and strand-displacement assays showed that in all the cases the trans-isomer is the one with superior binding affinities. Alternative versions, inspired by our first compounds here reported, may find applications in different fields such as chemical biology, nanotechnology and materials science.

Highlights

Light-driven control of oligonucleotide hybridization has demonstrated an enormous potential to regulate on-demand biological responses such as gene expression [1]
We explored two different types of photoswitches (Figure 1B): 1) second generation azobenzenes based on the tetra-orthofluoroazobenze developed by Hecht [43] and 2) hemithioindigos (HTI) rediscovered by Rück-Braun [44] and Dube [45], which have not been studied in the context of DNA/ RNA as molecular transducer yet
We focused on the tetra-ortho-fluoroazobenzene and the hemithioindigo (HTI) photoswitches; the latter has not been studied in the context of photoregulation of oligonucleotides before

Summary

Introduction

Light-driven control of oligonucleotide hybridization has demonstrated an enormous potential to regulate on-demand biological responses such as gene expression [1]. We explored two different types of photoswitches (Figure 1B): 1) second generation azobenzenes based on the tetra-orthofluoroazobenze (oF4Azo) developed by Hecht [43] and 2) hemithioindigos (HTI) rediscovered by Rück-Braun [44] and Dube [45], which have not been studied in the context of DNA/ RNA as molecular transducer yet. The large separation between the n → π* bands of the trans and the cis-forms (Δλ = 69 nm; Figure S24, Supporting Information File 1) did not lead to the quasi-quantitative conversion for the cis-isomer, as for the photoswitchable PNA monomer 1 and the molecular transducer [43,46].

Results

Conclusion