DNA Strand Base Research Articles

Study of Electrical and Thermoelectrical Properties of One Strand DNA Chain for Nanoscale Thermoelectric Applications

The concept of using DNA molecules for designing nano-scale electronic systems has attracted researcher’s attention due to the unique properties of DNA, such as self-assembly and self-recognition. Thus, increased number of studies, theoretically and experimentally, have been carried out to study the possibility of adopting DNA molecules in designing nanoscale thermoelectric devices. In this work, a general expression of the electron transmission probability that describes the electron transfer through one strand DNA chain has been derived using the steady-state-formalism by assuming one strand of DNA molecules as line model. The energy-dependent transmission was studied, then energy-and temperature-dependent Seebeck coefficient, and thermoelectric characteristics of four one strand DNA sequences: (A-A)10, (C-C)10, (G-G)10 and (T-T)10 are theoretically studied. According to the obtained results, it is found that the transmission behavior (magnitude and position) is varying with the type of DNA sequence. Also, the energy dependent Seebeck coefficient (S-E) curves clearly show a nonlinear energy-dependence, while the relationship between Seebeck coefficient and temperature (S-T) is linear. Thermoelectric power factor as a function of temperature was found to be enhanced with the temperature increment for the four types of DNA nucleobases. The highest values of thermoelectric power factor belong to thymine (120Wm-1K-2) and cytosine (60 Wm-1K-2), that nominate them as outstanding candidate thermoelectric materials to be adopted in the fabrication of one strand DNA-base nanoscale thermoelectric devices.

Nucleobase Recognition by Truncated α-Hemolysin Pores.

The α-hemolysin (αHL) protein nanopore has been investigated previously as a base detector for the strand sequencing of DNA and RNA. Recent findings have suggested that shorter pores might provide improved base discrimination. New work has also shown that truncated-barrel mutants (TBM) of αHL form functional pores in lipid bilayers. Therefore, we tested TBM pores for the ability to recognize bases in DNA strands immobilized within them. In the case of TBMΔ6, in which the barrel is shortened by ∼16 Å, one of the three recognition sites found in the wild-type pore, R1, was almost eliminated. With further mutagenesis (Met113 → Gly), R1 was completely removed, demonstrating that TBM pores can mediate sharpened recognition. Remarkably, a second mutant of TBMΔ6 (Met113 → Phe) was able to bind the positively charged β-cyclodextrin, am7βCD, unusually tightly, permitting the continuous recognition of individual nucleoside monophosphates, which would be required for exonuclease sequencing mediated by nanopore base identification.

Synthesis and Molecular-cellular Mechanistic Study of Pyridine Derivative of Dacarbazine.

Dacarbazine is an antitumor prodrug which is used for the treatment of malignant metastatic melanoma and Hodgkin's disease. It requires initial activation in liver through an N-demethylationreaction. The active metabolite prevents the progress of disease via alkylation of guanine bases in DNA strands. In order to investigate the importance of imidazole ring and its dynamictautomerization in anticancer activity of dacarbazine, a pyridine analog of this drug was synthesized and the cytotoxic activity and cellular-molecular mechanisms of action for this compound were compared with those of dacarbazine. EC50 values for dacarbazine and the pyridine analog were found to be 56 μM and 33 μM respectively. Both dacarbazine and the pyridine analog resulted in formation of reactive oxygen species (ROS) upon their addition to the isolated rat hepatocytes. They also decreased the mitochondrial membrane potential and causedlysosomal membrane rupture. Cytotoxicity was prevented by ROS scavengers and antioxidants. Cytotoxicity wasalso prevented by CYP450 inhibitors, lysosomalinactivators and MPT (Mitochondrial Permeability Transition Pore) blockers.

Colored petri nets to model gene mutation and amino acids classification

The genetic code is the triplet code based on the three-letter codons, which determines the specific amino acid sequences in proteins synthesis. Choosing an appropriate model for processing these codons is a useful method to study genetic processes in Molecular Biology. As an effective modeling tool of discrete event dynamic systems (DEDS), colored petri net (CPN) has been used for modeling several biological systems, such as metabolic pathways and genetic regulatory networks. According to the genetic code table, CPN is employed to model the process of genetic information transmission. In this paper, we propose a CPN model of amino acids classification, and further present the improved CPN model. Based on the model mentioned above, we give another CPN model to classify the type of gene mutations via contrasting the bases of DNA strands and the codons of amino acids along the polypeptide chain. This model is helpful in determining whether a certain gene mutation will cause the changes of the structures and functions of protein molecules. The effectiveness and accuracy of the presented model are illustrated by the examples in this paper.

Site-Specific Dynamics of Strands in ss- and dsDNA As Revealed by Time-Domain Fluorescence of 2-Aminopurine

It is well recognized that structure and dynamics of DNA strands guide proteins toward their cognate sites in DNA. While the dynamics is controlled primarily by the nucleotide sequence, the context of a particular sequence in relation to an open end could also play a significant role. In this work we have used the fluorescent analogue of adenine, 2-aminopurine (2-AP), to extract information on site-specific dynamics of DNA strands associated with 30-70 nucleotides length. Measurement of fluorescence lifetime and anisotropy decay kinetics in various types of DNA strands in which 2-AP was located in specific positions revealed novel insights into the dynamics of strands. We find that in single-stranded (ss) DNA, the extent of motional dynamics of the bases falls off sharply from the very end toward the middle of the strand. In contrast, the flexibility of the backbone decreases more gradually in the same direction. In double-stranded (ds) DNA, the level of base-pair fraying increases toward the ends in a graded manner. Surprisingly, the same is countered by the presence of ss-overhangs emanating from dsDNA ends. Moreover, the extent of concerted motion of bases in duplex DNA increased from the end to the middle of the duplex, a result which is both striking and counterintuitive. Most surprisingly, the two complementary strands of a duplex that were unequal in length exhibited differential dynamics: the longer one with overhangs showed a distinctly higher level of flexibility than the recessed shorter strand in the same duplex. All these results, taken together, provoke newer insights in our understanding of how different bases in DNA strands are endowed with specific dynamic properties as a function of their positions. These properties are likely to be used in facilitating specific recognitions of DNA bases by proteins during various DNA-protein interaction systems.

Charge Migration Mechanism in DNA Strands Elucidated by Electronic Structure Examinations

In order to establish the charge migration mechanism, we examined the electronic structure of bases in DNA strands by means of resonant photoemission spectroscopy near the Fermi level. Because the N atoms are only included in bases in DNA strands, the electronic orbital features of the bases can be specified selectively at the resonant excitation from the N core level to unoccupied states. On the obtained resonant photoemission spectra for both poly(dG) · poly(dC) and poly(dA) · poly(dT) DNAs, we observed a kinetic energy shift of N-KLL Auger electrons and an intensity enhancement of valence electrons. These results clearly show the localized unoccupied electronic states of the bases. Therefore, it is concluded that the charge hopping model is pertinent for the charge migration mechanism in DNA strands, when electrons pass through the unoccupied states.

Acridine Orange Sensitization and DNA Inhibition Effects on the Cyclic Voltammetry of Naphthoquinones Using Bare and DNA Modified Gold Electrodes

An ion pair mechanism is used to characterize the inhibition by DNA, and sensitization by acridine orange (AO) of the peak currents in the cyclic voltammetry (CV) of naphthoquinones with differing ionic substituents. Gold electrodes modified with adsorbed synthetic ′5-thiol-(GC)10 double strand DNA oligomers are used to study the redox activity of ferricyanide, 1,2-naphthoquinone-4-sulfonic acid sodium salt (NQS), 4-amino-1,2-naphthoquinone (ANQ), or 1,2-naphthoquinone (NQ) in the presence of AO. Parallel studies are performed using bare gold electrodes with double strand calf thymus DNA (CT-DNA) in the bulk solution. AO is known to bind intercalatively to DNA and is seen to sensitize the redox activity of ferricyanide or NQS with DNA either adsorbed on the electrode or present in the electrolyte. AO otherwise does not sensitize the peak currents in the CV of either ANQ or NQ regardless of the presence of DNA, nor does the DNA inhibit their CV, as it does the AO sensitized CV of the anions in the presence of DNA. The electroanalysis is done in pH 7 phosphate buffer with the solute and calf thymus double strand DNA base pair concentrations in the 10–3 molar range, and AO concentrations in the 10–4 molar range. The anion selective electrolytic sensitization combined with the intercalative property of AO may be applied to either the design of DNA based biosensors for the detection of anions, or DNA sensitive biosensors using AO as a marker.

Exposure of DNA bases induced by the interaction of DNA and calf thymus DNA helix-destabilizing protein.

The reaction of chloroacetaldehyde with adenine bases in DNA to give a fluorescent product was used to study the availability to intermolecular reaction of positions 1 and 6 of adenine in DNA complexes with calf thymus DNA helix-destabilizing protein. No inhibition of this reaction was observed when heat-denatured DNA was complexed with the protein at a protein/DNA weight ratio of 10:1, compared to free DNA. On the contrary, the same reaction was inhibited markedly for denatured DNA in the presence of calf thymus histone HI at protein/DNA weight ratio of 2:1. Furthermore, the exchange rate for hydrogens of amino and imide groups of DNA bases in DNA strands with deuterium in the solvent was totally unaffected upon complexing of DNA with the DNA helix-destabilizing protein as examined by stopped-flow ultraviolet spectroscopy. These results indicate that the DNA helix-destabilizing protein forms a complex with single-stranded DNA, leaving DNA bases uncovered by the protein. The fluorescence intensity of DNA pretreated with chloroacetaldehyde was amplified by nearly 3-fold upon addition of the DNA helix-destabilizing protein. The possibility of "unstacking" of DNA bases induced by the protein is discussed.