Enantioselective Incorporation of Azobenzenes into Oligodeoxyribonucleotide for Effective Photoregulation of Duplex Formation

Abstract

Various organic molecules have been introduced into oligodeoxyribonucleotides (ODNs) by means of linkers to provide new functionalities. [1] We already reported that the cis 3 trans isomerization of an azobenzene moiety in the side chain of ODNs could reversibly photoregulate the formation and dissociation of its duplex: a trans-azobenzene moiety in the ODN stabilizes the duplex, whereas the cis form destabilizes it. [2] By using this modified ODN as a modulator, a T7 DNA polymerase reaction could also be photoregulated. [3] For even more effective photoregulation, the change in melting temperature DT m induced by the trans 3cis isomerization should be enhanced. A promising strategy for this purpose is to introduce multiple azobenzene groups into the ODN. However, the modified ODN was previously synthesized from the corresponding racemic mixture of phosphoramidite monomers, which were obtained from a prochiral diol as starting material (Scheme 1 A). Thus, two diastereomers were inevitably produced. [4] Since their photoregulation capabilities are significantly different, [2a] the azobenzene moieties should be enantioselectively incorporated into the ODN for more effective photoregulation. With these racemic phosphoramidite monomers, it is practically impossible to synthesize diastereochemically pure ODNs containing multiple azobenzene groups, and hence the optically pure phosphoramidite monomer is essential.We chose threoninol as the linker (Scheme 1 B) for two reasons: 1) optically pure diols can be synthesized from the corresponding d-or l-threonine, and 2) perturbation of the framework of our previous prochiral linker (Scheme 1 A) is minimized. [5] Both l-and d-threoninol were used as optically pure linkers, and two azobenzene moieties were enantioselectively introduced. It was shown that a d-threoninoltethered azobenzene moiety induces much larger DT m on photoisomerization than does an l-threoninol-tethered one.

Alternating Hetero H Aggregation of Different Dyes by Interstrand Stacking from Two DNA–Dye Conjugates

“…Synthesis of the modified DNA involving dyes: The modified DNA molecules carrying A , M , N , and S residues were synthesized with an automated DNA synthesizer by using the corresponding phosphoramidite monomer prepared according to previous papers,6, 9, 20 and conventional ones. All the modified DNA molecules listed in Scheme were purified by reversed‐phase HPLC and characterized by MALDI‐TOF mass spectrometry.…”

Circular‐Polarization‐Induced Enantiomeric Excess in Liquid Crystals of an Achiral, Bent‐Shaped Mesogen

“…The higher‐temperature, liquid‐crystalline SmC A phase is a fluid phase in which two axially twisted conformers interchange such that the system is either achiral or racemic. Photochromic azobenzenes have been utilized extensively in supramolecular chemistry, catalysis, and materials science because of their efficient, reversible trans – cis photoisomerization, which leads to large changes in molecular geometry 24. It is well known that rod‐like, azo‐containing molecules tend to reorient under linearly polarized light irradiation to the direction perpendicular to the polarization 25.…”

Photoswitching of Site-Selective RNA Scission by Sequential Incorporation of Azobenzene and Acridine Residues in a DNA Oligomer

“…Adjacent to X 1 , an azobenzene residue ( Y D ) was also introduced as the 19th residue. This conjugate of D-threoninol and azobenzene is known to be a good photoswitch of duplex formation [13]. When the corresponding simple acridine-modified DNA 3 is hybridized to the complementary substrate RNA 1 , the target U-19 residue alone remains unpaired, and the 5′-phosphate linkage (indicated by the arrow in Figure 1) of the target is efficiently cleaved by Lu(III) ion in the aid of acid catalysis by the acridine.…”

“…The oligonucleotide 9 also bears X 3 and Y D in the middle, but Y D is inserted in the 5′ side of X 3 . A previous study has shown that the steric effect caused by the isomerization of azobenzene strongly depends on the regiochemical conformation of the threoninol backbone [13]. For the purpose of comparison, Y L , a diastereomer of Y D , was prepared and incorporated into oligonucleotides 6 and 7 .…”

“…The synthetic route for the phosphoramidite of X 2 is described in [11]. The phosphoramidites for Y D and Y L were synthesized according to [13]. All the oligonucleotides were synthesized on an ABI 3400 DNA Synthesizer in 1  μ mol scale.…”