A cooperated experimental and computational investigation on sulfonyl amidine formation from thioamides and sulfonyl azides is described. The data support a non-concerted two-step pathway for the coupling reaction and also indicate that dipole moment of thioamide and electrophilicity of sulfonyl azide would be significant factors for the reaction efficiency. A simple reactivity prediction of the coupling reaction was demonstrated by preliminary in silico evaluation for these factors, by which we successfully picked up a good pair of reactants with a high reactivity among several thioamides and sulfonyl azides in stock.Download high-res image (52KB)Download full-size image

We describe artificial DNA molecules exclusively consisting of four types of alkynyl C-nucleotides with nonnatural bases. The artificial DNA exhibited almost the same characteristics as natural DNA, such as in regard to the stepwise duplex and triplex formation and the right-handed higher-order structure with an antiparallel alignment fashion.

We report bending flexibility of damaged duplexes possessing an apurinic/apyrimidinic (AP) site analogue, a cyclobutane pyrimidine dimer (CPD), and a pyrimidine(6-4)pyrimidone photoproduct (6-4PP). Based on the electrochemical evaluation on electrodes, the duplex flexibilities of the lesions increased in the following order: CPD < AP < 6-4PP. We discussed the possibility that the emerging local flexibility might be a good sign for UV-damaged DNA-binding proteins on duplexes.

We propose linear end-to-end assemblies of short DNA duplexes based on β-cyclodextrin–adamantane complexation. The assembled duplexes exhibited increased Tm values compared with those of the corresponding natural hybrids. Competition experiments with external guest molecules showed a substantial decrease in Tm of the terminal modified duplexes, suggesting the viability of inter-duplex complexation.

We report a coupling reaction of thioamides and sulfonyl azides to generate sulfonyl amidines in the absence of any activation additives. The reaction progresses in various solvents under mild conditions. Water exhibits the highest performance with respect to efficiency.

We describe syntheses and electrochemical properties of a new class of aminopyrimidinone derivatives: 2-amino-4-(3′,4′-dimethoxyphenyl)-6-pyrimidinone, 2-amino-4-(3′,4′-dihydroxyphenyl)-6-pyrimidinone, 2,4-diamino-5-(3′,4′-dimethoxyphenyl)-6-pyrimidinone, 2,4-diamino-5-(3′,4′-dihydroxyphenyl)-6-pyrimidinone, and 4-amino-5-(3′,4′-dihydroxyphenyl)-2,6-pyrimidinione, three of which possess a catechol unit as an oxidation-active moiety for developing electrochemically detectable abasic-site binders. These compounds were synthesized via a pyrimidine-ring forming reaction with guanidine. Cyclic voltammetry measurements revealed that the catechol-bearing derivatives showed oxidation potentials lower than that of DNA, indicating that they satisfied the requirements for the purpose.

APOBEC3G catalyzes deamination of cytosines in HIV-1 genome, and restricts the HIV-1 infection. Here, we propose a picomole-scale assay for the detection of DNA deamination catalyzed by APOBEC3G. Our results show the suitability of the developed method for a time course analysis of enzyme-catalyzed DNA modifications.

Ferrocene-modified DNA probes formed fully matched duplexes and bulge-containing ones with wild-type and insertion/deletion-type complements of clinical importance, respectively. Cyclic voltammetry measurements revealed that the bulge-containing duplexes showed an increased flexibility compared to the fully matched duplexes. The difference in the bending elasticity could be read out electrochemically by square wave voltammetry.

APOBEC3G catalyzes deamination of cytosines in HIV-1 genome, and restricts the HIV-1 infection. Here, we propose a picomole-scale assay for the detection of DNA deamination catalyzed by APOBEC3G. Our results show the suitability of the developed method for a time course analysis of enzyme-catalyzed DNA modifications.

We report bending flexibility of damaged duplexes possessing an apurinic/apyrimidinic (AP) site analogue, a cyclobutane pyrimidine dimer (CPD), and a pyrimidine(6-4)pyrimidone photoproduct (6-4PP). Based on the electrochemical evaluation on electrodes, the duplex flexibilities of the lesions increased in the following order: CPD < AP < 6-4PP. We discussed the possibility that the emerging local flexibility might be a good sign for UV-damaged DNA-binding proteins on duplexes.

We propose linear end-to-end assemblies of short DNA duplexes based on β-cyclodextrin–adamantane complexation. The assembled duplexes exhibited increased Tm values compared with those of the corresponding natural hybrids. Competition experiments with external guest molecules showed a substantial decrease in Tm of the terminal modified duplexes, suggesting the viability of inter-duplex complexation.

Ferrocene-modified DNA probes formed fully matched duplexes and bulge-containing ones with wild-type and insertion/deletion-type complements of clinical importance, respectively. Cyclic voltammetry measurements revealed that the bulge-containing duplexes showed an increased flexibility compared to the fully matched duplexes. The difference in the bending elasticity could be read out electrochemically by square wave voltammetry.

We describe artificial DNA molecules exclusively consisting of four types of alkynyl C-nucleotides with nonnatural bases. The artificial DNA exhibited almost the same characteristics as natural DNA, such as in regard to the stepwise duplex and triplex formation and the right-handed higher-order structure with an antiparallel alignment fashion.

We report a coupling reaction of thioamides and sulfonyl azides to generate sulfonyl amidines in the absence of any activation additives. The reaction progresses in various solvents under mild conditions. Water exhibits the highest performance with respect to efficiency.