Chemistry of Sequence-Dependent Remote Guanine Oxidation: Photoreaction of Duplex DNA Containing Cyanobenzophenone-Substituted Uridine

Chemistry of Sequence-Dependent Remote Guanine Oxidation:  Photoreaction of Duplex DNA Containing Cyanobenzophenone-Substituted Uridin

Modulation of DNA-Mediated Hole-Transport Efficiency by Changing Superexchange Electronic Interaction

Modulation of DNA-Mediated Hole-Transport Efficiency by Changing Superexchange Electronic Interactio

Synthesis of DNA Oligomers Containing Modified Uracil Possessing Electron-Accepting Benzophenone Chromophore

Synthesis of DNA Oligomers Containing Modified Uracil Possessing Electron-Accepting Benzophenone Chromophor

<i>N</i>²-Phenyldeoxyguanosine: Modulation of the Chemical Properties of Deoxyguanosine toward One-Electron Oxidation in DNA

We have shown here that (1) substitution of an exocyclic amino group of dG is effective in modulating the chemical properties of dG toward one-electron oxidation and (2) decomposition of the guanine radical cation was effectively suppressed near dPhG. These results indicate that dPhG is a prototype of nucleosides functioning as an intrinsic antioxidant of duplex DNA toward one-electron oxidation

Design of a Hole-Trapping Nucleobase: Termination of DNA-Mediated Hole Transport at <i>N</i>²-Cyclopropyldeoxyguanosine

Design of a Hole-Trapping Nucleobase:  Termination of DNA-Mediated Hole Transport at N2-Cyclopropyldeoxyguanosin

Direct Chemical Evidence for Charge Transfer between Photoexcited 2-Aminopurine and Guanine in Duplex DNA

Photoexcited 2-aminopurine (Ap*) is extensively exploited as a fluorescent base analogue in the study of DNA structure and dynamics. Quenching of Ap* in DNA is often attributed to stacking interactions between Ap* and DNA bases, despite compelling evidence indicating that charge transfer (CT) between Ap* and DNA bases contributes to quenching. Here we present direct chemical evidence that Ap* undergoes CT with guanine residues in duplex DNA, generating oxidative damage at a distance. Irradiation of Ap in DNA containing the modified guanine, cyclopropylguanosine (CPG), initiates hole transfer from Ap* followed by rapid ring opening of the CPG radical cation. Ring opening accelerates hole trapping to a much shorter time regime than for guanine radicals in DNA; consequently, trapping effectively competes with back electron transfer (BET) leading to permanent CT chemistry. Significantly, BET remains competitive, even with this much faster trapping reaction, consistent with measured kinetics of DNA-mediated CT. The distance dependence of BET is sharper than that of forward CT, leading to an inverted dependence of product yield on distance; at short distances product yield is inhibited by BET, while at longer distances trapping dominates, leading to permanent products. The distance dependence of product yield is distinct from forward CT, or charge injection. As with photoinduced charge transfer in other chemical and biological systems, rapid kinetics for charge injection into DNA need not be associated with a high yield of DNA damage products

Photoswitchable Molecular Glue for DNA

DNA molecular glue is a small synthetic ligand that can adhere two single-stranded DNAs that do not spontaneously hybridize with each other. For reversible control of DNA hybridization by an external light stimulus, we have developed a photoswitchable molecular glue for DNA. The photoswitchable molecular glue, NCDA, consists of two guanine-recognizing naphthyridine moieties connected with a photochromic azobenzene unit. Azobenzene undergoes a reversible cis/trans isomerization by photoirradiation, which changes the relative orientations and positions of the naphthyridine moieties, resulting into photoswitching of NCDA binding to the DNA containing GG-mismatch. NCDA in the cis configuration binds to a GG-mismatch sequence and induces the formation of the DNA duplex. Using the photoswitchable binding property of NCDA, the hybridization event of two natural unmodified DNAs can be reversibly controlled by an external light stimulus

Hole Trapping at <i>N</i>⁶-Cyclopropyldeoxyadenosine Suggests a Direct Contribution of Adenine Bases to Hole Transport through DNA

Recent studies predict that adenine radical cation (A•+) contributes to the hole-trapping process through long A/T sequences and exists as a real chemical intermediate. However, the experimental evidence for the existence of A•+ has not been observed in the DNA-mediated hole transport reaction. To examine the direct contribution of A•+, we have developed a novel hole-trapping nucleobase N6-cyclopropyldeoxyadenosine (dCPA) which possesses a cyclopropyl group as a radical trapping device. One-electron oxidation of dCPA revealed that dCPA radical cation undergoes a rapid cyclopropane ring opening. With the use of the dCPA-containing DNA, we have demonstrated that the migrating hole was trapped at CPA incorporated into a long A/T bridge between two GG sites. The present results indicate that nucleobases possessing ionization potential higher than that of dG, such as dA, are able to participate directly in the multistep hopping mechanism

Photoregulation of a Peptide−RNA Interaction on a Gold Surface

The discovery of riboswitching has accelerated research on the interaction between RNA and small organic compounds. It will be important for biologists to artificially and reversibly control gene expression in vivo through the interaction of RNA and small molecules. In this paper, we report that RNA aptamers obtained from in vitro selection in which a photoresponsive short peptide containing the azobenzene moiety with flanking arginine residues on both sides as a ligand provided reversible binding to the ligand peptide immobilized onto the gold surface. We designed and synthesized a photoresponsive short peptide that can interact with RNA, can convert its conformation reversibly by photoirradiation, and can be produced on a large scale for in vitro selection. The RNA pool contained N70 random sequences, and after the eighth cycle, we identified RNA aptamers showing the Kd of about a few micromolar. A surface plasmon resonance (SPR) experiment revealed that RNA aptamers could bind to the trans-isomer of the peptide immobilized on the gold surface but not to the cis-peptide isomerized by photoirradiation with 360 nm light to the gold surface. The SPR signals were recovered after photoirradiation with 430 nm light, leading to isomerization of the peptide from cis to trans

Effects of the Photooxidant on DNA-Mediated Charge Transport

A direct comparison of DNA charge transport (CT) with different photooxidants has been made. Photooxidants tested include the two metallointercalators, Rh(phi)2(bpy‘)3+ and Ru(phen)(bpy‘)(dppz)2+, and three organic intercalators, ethidium (Et), thionine (Th), and anthraquinone (AQ). CT has been examined through a DNA duplex containing an A6-tract intervening between two 5‘-CGGC-3‘ sites with each of the photooxidants covalently tethered to one end of the DNA duplex. CT is assayed both through determination of the yield of oxidative guanine damage and, in derivative DNA assemblies, by analysis of the yield of a faster oxidative trapping reaction, ring opening of N2-cyclopropylguanine (dCPG) within the DNA duplex. We find clear differences in oxidative damage ratios at the distal versus proximal 5‘-CGGC-3‘ sites depending upon the photooxidant employed. Importantly, nondenaturing gel electrophoresis data demonstrate the absence of any DNA aggregation by the DNA-bound intercalators. Hence, differences seen with assemblies containing various photooxidants cannot be attributed to differential aggregation. Comparisons in assemblies using different photooxidants thus reveal characteristics of the photooxidant as well as characteristics of the DNA assembly. In the series examined, the lowest distal/proximal DNA damage ratios are obtained with Ru and AQ, while, for both Rh and Et, high distal/proximal damage ratios are found. The oxidative damage yields vary in the order Ru > AQ > Rh > Et, and photooxidants that produce higher distal/proximal damage ratios have lower yields. While no oxidative DNA damage is detected using thionine as a photooxidant, oxidation is evident using the faster cyclopropylguanosine trap; here, a complex distance dependence is found. Differences observed among photooxidants as well as the complex distance dependence are attributed to differences in rates of back electron transfer (BET). Such differences are important to consider in developing mechanistic models for DNA CT