The kinetics of RNase H promoted cleavage of the RNA strand in the antisense oligonucleotide (AON)–RNA hybrid duplexes, with the 3 -end of the AON strand tethered with cholic acid (2), its triacetate (3), cholesterol (4) or dipyridophenazine (5), have been investigated by changing the concentration of both the AON and the RNA strands, while keeping the enzyme and the buffer concentration consta...

Synthetic RNA duplexes that are substrates for Dicer are potent triggers of RNA interference (RNAi). Blunt 27mer duplexes can be up to 100-fold more potent than traditional 21mer duplexes. Not all 27mer duplexes show increased potency. Evaluation of the products of in vitro dicing reactions using electrospray ionization mass spectrometry reveals that a variety of products can be produced by Dic...

To understand why the RNA-RNA duplexes in general has a higher thermodynamic stability over the corresponding DNA-DNA duplexes, we have measured the pK(a) values of both nucleoside 3',5'-bis-ethyl phosphates [Etp(d/rN)pEt] and nucleoside 3'-ethyl phosphates [(d/rN)pEt] (N = A, G, C, or T/U), modeling as donors and acceptors of base pairs in duplexes. While the 3',5'-bis-phosphates, Etp(d/rN)pEt...

The crystal structure of the duplex formed by oligo(2',3'-dideoxy-beta-d-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M., Pallan,P.S., Pattanayek,R., Wilds,C.J., Lubini,P., Minasov,G., Dobler,M., Leumann,C.J. and Eschenmoser,A. (2006) Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. J. Am. Chem....

Two phosphate modifications were introduced into the DNA backbone using Staudinger reaction between 3’,5’-dinucleoside ?-cyanoethyl phosphite triester formed during synthesis and sulfonyl azides, 4-(azidosulfonyl)- N,N,N -trimethylbutan-1-aminium iodide (N+ azide) or p -toluenesulfonyl (tosyl Ts) azide, to provide either a zwitterionic phosphoramidate with N+ modification negatively charged for...

Although proteins mediate highly ordered DNA organization in vivo, theoretical studies suggest that homologous DNA duplexes can preferentially associate with one another even in the absence of proteins. Here we combine molecular dynamics simulations with single-molecule fluorescence resonance energy transfer experiments to examine the interactions between duplex DNA in the presence of spermine,...

Pressure perturbation differential scanning calorimetry was used to determine thermal expansion coefficients and thus temperature-induced volume changes of DNA duplexes differing in their GC/AT content. It was shown that the temperature-induced unfolding of the DNA duplexes proceeds with a significant increase of the thermal expansion coefficient and the partial volume of the DNA. Unusually, la...

DNA-mediated charge transport (CT) chemistry is sensitive to DNA structure and base pair stacking. In an electrochemical assay based upon DNA CT, DNA-modified electrode surfaces are used to examine the electrochemical reduction of methylene blue (MB), a small molecule that binds to the DNA film by intercalation. Here electrochemically we probe CT in the three primary conformations of double-str...

More than 50 years after Watson and Crick unraveled the secondary structure of the canonical B-formDNA duplex, the function of the pyrimidine–purine nucleobase pairing and the importance of the charged phosphodiester backbone are well established. However, the chemical and evolutionary necessity for the rather complicated deoxyribose and ribose moiety in the backbone of DNA and RNA, respectivel...