Photoswitchable 2‐Phenyldiazenyl‐Purines and their Influence on DNA Hybridization

Abstract

Recently, photochromic derivatives of nucleobases have drawn attention for regulating oligonucleotide hybridization with light for photopharmacological applications. The nucleobase moiety provides attractive interaction for hybridization, whereas the photochromic moiety can alter the interaction upon irradiation due to conformational changes. Herein we report the synthesis of 2-phenyldiazenyl-substituted 2'-deoxyadenosine (dA Azo) and 2'-deoxyguanosine (dG Azo) and investigate their influence in a DNA context by UV/Vis absorption, fluorescence and CD spectroscopies. For comparison, the literature-known azobenzene C-nucleoside DNAzo was used as a reference system. It could be shown that photochromic purines improve overall hybridization affinity compared to azobenzene C-nucleosides. In particular, 2'-deoxyadenosine analogue dA Azo increases melting temperatures by 7.5°C in the favored trans state with 86 % of the switching efficiency of the reference system.

Photochemical modifications for DNA/RNA oligonucleotides

“…17I and J). 10 G Azo has been developed by Ogasawara and used as a photoresponsive 5 0 -cap of mRNA in vivo to control protein expression. 142 Reaction characteristics.…”

“… 130,131,136 dA Azo and dG Azo decreased the T m of 10-bp DNA duplexes by 10–13 °C compared with 16 °C of m -Azo. 10 …”

“…[1][2][3][4] These controls rely on photoconvertible groups that undergo structural changes upon irradiation by light. [5][6][7][8][9][10] Light can be readily applied to and removed from a reaction, and the wavelength, localization, and intensity of the light can be precisely controlled. 11,12 Thus, light offers distinct advantages in triggering and controlling reactions, compared with other more common methods such as chemical inhibition, rapid mixing, temperature-, salt-or pH-jumps.…”

Photoresponsive Control of G-Quadruplex DNA Systems

“…While being an emerging area, studies concerning the photoregulation of G4 structures are less common than examples of photoregulation of duplex DNA hairpins. − In this Perspective, we focus our attention on the most recent examples of photoresponsive G4-based systems and the strategies used to engineer these systems toward a variety of applications. For a more comprehensive overview regarding photoresponsive control of oligonucleotide structures, the reader is referred to another recent review …”

Chemo-enzymatische Synthese lichtaktivierbarer RNA & Synthese lichtregulierbarer Oligonukleotide zur spektroskopischen Strukturaufklärung

“…Allerdings wurde durch die Substitution an Position 2 die Duplexstabilität erhöht, sodass die Belichtung nur bedingt Isomerisierungseffekte zeigte. [315] Asanuma et al präsentierten 2'-Azobenzol-modifiziertes Uridin (2'-Azo-rU) zur lichtinduzierten Duplexdestabilisierung. [316] Neben Nukleobasen-Derivaten, können auch unnatürliche photochrome Nukleoside in Oligonukleotide eingebaut werden (Abb.…”