Complementary Nucleic Acid Bases Research Articles

DNA structure and dynamics: Potential of interactions between two complementary DNA bases

AbstractSpecific interaction between two complementary nucleic acid bases, in which adenine forms two hydrogen bonds with thymine and guanine forms three hydrogen bonds with cytosine, is of great interest because it stabilizes the double helical DNA structure and because it determines the dynamics of the base pair opening that in turn is considered as one of important elements of the process of the DNA–protein recognition. To obtain the form of the potential of the interaction, investigators use many different methods including the most accurate ab initio quantum‐chemical calculations, approximate method of atom–atom potential functions, approximate mathematical formulas like the Morse potential, or empirical potentials. In this article, we derive a new mathematical formula of the potential. The formula is well grounded and advantageously differs from others because of its simplicity and convenience in practice. To derive the formula, we use a simple mechanical analog of two complementary DNA bases that consists of two coupled pendulums oscillating in the horizontal plane. We illustrate the applications of the formula to study small amplitude oscillations of the DNA complementary bases. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

Calculation and analysis of vibrational spectra of adenine–thymine, guanine–cytosine, and adenine–uracil complementary pairs in the condensed state

We have calculated the frequencies of the normal vibrations of the complementary nucleic acid base pairs adenine–thymine, guanine–cytosine, adenine–uracil, corresponding to the Watson–Crick structure, and the adenine–uracil pair, corresponding to the Hoogsteen structure, in condensed states and we interpret the spectra. We determine the contributions of hydrogen bonds to the vibrational modes of the complementary pairs. We have analyzed the nature of the relative displacements of the nucleic acid bases as integral molecular units along the hydrogen bonds. We show the role of hydrogen bonds in tautomeric interconversions of complementary nucleic acid base pairs.

Hydrogen bonding interaction between aminopurinethiol-monolayers and oligonucleotides by QCM and XPS measurements

Selective detection of oligonucleotides on the gold surface modified with a monomolecular layer of aminopurinethiols was demonstrated. A quartz crystal microbalance (QCM) measurement is suitable to detect interactions between the complementary nucleic acid base in solution and the aminopurinethiolate monolayer on gold. 6-Amino-8-purinethiol monolayer had specific interactions with polythymidylic acid (Poly(T)) in solution, whereas it had very weak interaction with polycytidylic acid (Poly(C)). Poly(T) (thymine species) in solution created hydrogen bonding interaction with the 6-amino-8-purinethiol monolayer, because 6-amino-8-purinethiol showed adenine-like conformation on the gold surface. In the case of 2-amino-6-purinethiol monolayer, niether Poly(T) nor Poly(C) were recognized on the substrate. Since 2-amino-6-purinethiol monolayer adsorbed on the gold surface in the parallel direction of the long axis of molecules, the recognition sites of the molecules were blocked. Hydrogen bonding interactions of the 6-amino-8-prinethiol monolayer-base species were identified by X-ray photoelectron spectroscopic (XPS) measurements.

Electrochemical responses of cytochrome c on gold electrodes modified with nucleic acid base derivatives–electrochemical and quartz crystal microbalance studies

The electrochemical responses of cytochrome c on the gold electrodes modified with nucleic acid base derivatives such as 2-amino-6-purinethiol, 2-amino-6-mercaptopurine riboside, 6-amino-8-purinethiol and 2-thiouracil were investigated. The monolayers of 2-amino-6-purinethiol and 6-amino-8-purinethiol on gold can promote the electron transfer between cytochrome c in solution and gold electrode like that of well-known promoters such as pyridylthiol derivatives and carboxylic acid terminated alkanethiols, as reported previously. However, in the case of 2-amino-6-mercaptopurine riboside modified gold electrode, the redox response of cytochrome c was completely inhibited, because a bulky ribose group inhibited the promoting ability. We also confirmed that the 2-thiouracil on gold electrode can facilitate the electron transfer between cytochrome c and gold electrode. The redox response of cytochrome c on 6-amino-8-purinethiol modified gold electrode was inhibited effectively by forming a hydrogen bonded complex with a complementary nucleic acid base derivative, thymidine. However, in the cases of 2-amino-6-purinethiol and 2-thiouracil modified gold electrodes, the redox response of cytochrome c was not inhibited by thymidine treatment. These phenomena should reflect the difference of adsorbed direction between 2-amino-6-purinethiol and 6-amino-8-purinethiol on gold and the unsuitable matching of thiouracil adsorbed on gold with thymidine in solution.

FT-SERS Studies on Molecular Recognition Capabilities of Monolayers of Novel Nucleolipid Amphiphiles

The molecular recognition effect in nucleic acids was simulated in the monolayers formed by six novel nucleolipid amphiphiles. Fourier transform surface-enhanced Raman scattering (FT-SERS) technique was introduced into the research area of molecular recognition occurring in an interface system. High-quality FT-SERS spectra of a single Langmuir−Blodgett (LB) monolayer of the nucleolipid amphiphiles were obtained. Characteristic vibrational modes of the corresponding complementary nucleic acid bases, which transferred along with the monolayers of nucleolipid amphiphiles into the LB films, were clearly seen. The mechanism of molecular recognition through multiple hydrogen bonds between complementary bases was described. It was proved that this technique can be used as a powerful tool for studying molecular recognition in interface systems because of its high sensitivity.

Adenosine-Induced Changes of the Phase Transition of Poly(6-(acryloyloxymethyl)uracil) Aqueous Solution

Poly(6-(acryloyloxymethyl)uracil) (PAU) having uracil moieties as side chains was synthesized by ordinary radical polymerization to investigate its molecular discrimination for soluble nucleic acid bases in terms of phase transition changes of the polymer aqueous solution. PAU itself in distilled water formed a precipitate due to the polymer complexes at lower temperatures and changed drastically to become water-soluble above a characteristic transition temperature, showing an upper critical solution temperature (UCST). The phase transition behavior was shifted to lower temperatures with increasing concentrations of adenosine (Ado), which is the complementary nucleic acid base to uracil moiety. Ado might interact specifically with uracil moieties of the polymers, preventing the formation of the polymer complex at lower temperatures. Such changes were not observed in PAU aqueous solution containing guanosine (Guo). Additions of Ado and Guo exerted different effects to phase transition changes of the polymer. Moreover, addition of poly(adenylic acid) (Poly(A)) lowered remarkably the transition behavior of PAU solution as compared with Ado addition. It was conceivable that PAU and Poly(A) formed stable polymer complexes, assuming soluble states in even cold water. PAU changed its phase-transition temperature in response to species of the additive materials, demonstrating the specific molecular discrimination in aqueous milieu.

Electrochemical behavior of gold electrodes modified with aminopurinethiol derivatives

The electrochemical properties of gold electrodes modified with 2-amino-6-purinethiol and 6-amino-8-purinethiol were investigated. The aminopurinethiolate monolayers could facilitate the electron transfer between cytochrome c in solution and a gold electrode in the same way as well-known promoters such as pyridylthiol derivatives and carboxylic acid terminated alkanethiols as reported previously. The redox response of cytochrome c on a 6-amino-8-purinethiol modified gold electrode was inhibited effectively by forming a hydrogen bonded complex with a complementary nucleic acid base derivative, thymidine. However, in the case of a 2-amino-6-purinethiol modified gold electrode, an inhibition of the redox response of cytochrome c by thymidine treatment was not observed. These phenomena reflect the difference of direction of each of the adsorbed molecules.

Antisense strategies and therapeutic applications.

The concepts underlying the antisense approach to disease therapy are discussed, and potential applications are examined. Antisense therapeutic agents bind to DNA or RNA sequences, blocking the synthesis of cellular proteins with unparalleled specificity. Transcription and translation are the two processes with which the agents interfere. There are three major classes of antisense agents: antisense sequences, commonly called antisense oligonucleotides; antigene sequences; and ribozymes. Antisense sequences are derivatives of nucleic acids that hybridize cytosolic messenger RNA (mRNA) sense strands through hydrogen bonding to complementary nucleic acid bases. Antigene sequences hybridize double-stranded DNA in the nucleus, forming triple helixes. Ribozymes, rather than inhibiting protein synthesis simply by binding to a single targeted mRNA, combine enzymatic processes with the specificity of antisense base pairing, creating a molecule that can incapacitate multiple targeted mRNAs. Antisense therapeutic agents are being investigated in vitro and in vivo for use in treating human immunodeficiency virus infection, hepatitis B virus infection, herpes simplex virus infection, papillomavirus infection, cancer, restenosis, rheumatoid arthritis, and allergic disorders. Although many results are preliminary, some are promising and have led to clinical trials. A major goal in developing methods of delivering antisense agents is to reduce their susceptibility to nucleases while retaining their ability to bind to targeted sites. Modification of the phosphodiester linkages in oligonucleotides can lend the sequences enzymatic stability without affecting their binding capacities. Carrier systems designed to protect the antisense structure and improve passage through the cell membrane include liposomes, water-soluble polymers, and nanoparticles. The pharmacokinetics of antisense agents are under investigation. Antisense therapeutic agents have the potential to become an integral part of medicinal regimens.

Functional monomers and polymers. CXXXII. Template polymerization of methacrylamide derivatives containing nucleic acid bases

AbstractFree‐radical polymerizations of methacrylamide derivatives containing nucleic acid bases were studied in the presence of the polymethacrylamide having complementary nucleic acid bases as template polymers. The rate of the polymerization did not show remarkable difference in the presence or the absence of the template polymer. A stable polymer complex, however, was precipitated from the polymerization system, and was found to be different in a thermal analysis from the polymer complex which was obtained by mixing of the complementary polymers in solution. Free‐radical copolymerizations in the presence of the template polymers also supported the template polymerization.

Synthesis and Properties of Hydrophilic Copolymers Containing 5-Fluorouracil, Thymine, or Adenine

Abstract Hydrophilic copolymers containing 5-fluorouracil (5-FU), thymine, or adenine were prepared by the free-radical copolymerization of methacryloyl-type monomers containing them with water-soluble vinyl monomers such as acrylic acid, methacrylic acid, vinylpyrroli-done, acrylamide, and 4(5)-vinylimidazole with AIBN as initiator. Complex formation between the copolymers and RNA and between the copolymers having complementary nucleic acid bases in aqueous solution and a DMSO-ethylene glycol was studied by means of UV spectroscopy. These copolymers were found to release the N-hydroxyethyl derivatives of 5-FU, thymine, or adenine by hydrolysis of the ester of the polymer side chain under mild conditions. The effects of the kind of water-soluble comonomer, temperature, pH, and the imidazole group as catalyst on the hydrolysis of the ester are discussed.

Functional monomers and polymers, 115. Permeability of hydrogel membranes consisting of copolymers containing pendant nucleic acid bases

AbstractHydrogel membranes consisting of copolymers from 2‐hydroxyethyl methacrylate (1a) and vinyl monomers (1b, 2b, 1c, 2c) containing nucleic acid bases such as adenine and uracil, were prepared by casting technique. The permeability measurement of these membranes for adenine and uracil revealed a selective transport which depends on the copolymer composition of the membranes and the permeation conditions. Transport of adenine based on the difference of proton concentration was also observed. The specific interaction between complementary nucleic acid bases seems to play an important role in the permeation behavior.

Functional monomers and polymers. LXXXIV. On the specific base‐base interaction between polymers having complementary nucleic acid bases

Functional monomers and polymers. LXXXIV. On the specific base‐base interaction between polymers having complementary nucleic acid bases

Functional Monomers and Polymers Containing Nucleic Acid Bases: Experiments on Template Polymerization

Abstract In order to see how the specific base-base interactions observed between complementary nucleic acid bases can be realized for free-radical polymerization systems, the template polymerization of methacrylate type monomers containing nucleic acid bases in the presence of template polymers containing complementary bases was studied. Stereoregular polymers were chosen as the template polymers. The radical copolymerization of the monomers containing complementary nucleic acid bases was also studied in different solvents.

Functional monomers and polymers. XXXXI. Template polymerization of methacryloyl‐type monomers containing nucleic acid bases

AbstractIn due consideration of the specific base–base interaction that exists between nucleic acid molecules, the free radical polymerization of N‐β‐methacryloyloxyethyl derivatives of adenine, thymine, and theophylline initiated by azobisisobutyronitrile (AIBN) was studied in the presence of N‐β‐methacryloyloxyethyl‐type polymers which have complementary nucleic acid bases as template polymers. The rate of polymerization of N‐β‐methacryloyloxyethyladenine was accelerated when poly(N‐β‐methacryloyloxyethyluracil) or ‐thymine was present in the polymerization system. The effect of the stereoregularity of the template polymers, as well as polymerization temperature and the sort of solvents used on the rate of polymerization, was studied and discussed in some detail. The results suggest that the interaction between complementary bases plays a role in template polymerization behavior.

Functional monomers and polymers. XXXXVII. Complex formation of stereoregular methacryloyl‐type polymers containing nucleic acid bases

AbstractThe complex formation between a poly(N‐β‐methacryloyloxyethyl) derivative of adenine with one of thymine or uracil was studied in dimethyl sulfoxide and ethylene glycol mixture by ultraviolet (UV) spectroscopy. For the polymer pairs containing complementary nucleic acid bases both hypochromicity and hyperchromicity were found. Stereoregularity of the polymers, as well as the conditions for measurement of, for example, solvent, temperature, and time, affected the complex formation. Both inter‐ and intramolecular interaction of polymers in solution were discussed in some detail.

Functional monomers and polymers. XXXXVI. A copolymerization study of methacryloyl‐type monomers containing nucleic acid bases in chloroform solution

AbstractBehavior of the free radical copolymerization of N‐β‐methacryloyloxyethyl derivatives of adenine with that of thymine was studied in chloroform solution, taking account of the specific base‐base interaction of these monomers. Hydrogen bonding interaction between such monomers was observed by NMR spectroscopy. The acceleration of copolymerization was found to be greater either at lower monomer concentration or at lower polymerization temperature. When N‐β‐methacryloyloxyethylcarbazole was used as a comonomer, the rate of copolymerization showed a similar trend as in the case of usual free radical copolymerizations. From r1 and r2 values obtained, the copolymerization was found to be alternating, particularly in the case of copolymerization between monomers having complementary nucleic acid bases. The results suggest that the hydrogen bonding interaction between adenine and thymine plays a role in the propagation step.

Saturation Transfer in NMR and its Application to the Studies on the Exchange Processes of Biological Substances

The substance exchanging between two chemically different sites A and B gives two separate NMR signals at νA and νB, if the exchange rate is slower enough than the frequency separation ΔνAB. When the sample is irradiated at the frequency νB, the signal intensity of A occasionally becomes weaker or disappears. This phenomenon is called saturation transfer in NMR and is used to determine the sites and rate of the exchange process. This technique is only applicable when the life time of exchange is between the inverse of ΔνAB and the spin lattice relaxation time T1.By using this technique we found that there is direct proton exchange between the complementary nucleic acid bases in organic solvents. When the signal of the amino protons of an adenine derivative is irradiated, the imino proton signal of an uracil derivative disappears. By quantitative analysis following the Forsen and Hoffman's treatment, it was found that the exchange occurs ten times in a second at room temperature.Other applications related to biological systems are reviewed: the electron exchange between cytochromes and the proton exchange between peptides and solvent water. The rates of following reactions were examined: the synthesis of ATP from AMP and inorganic phosphate by ATPase, the disproportionation of two ADP to ATP and AMP by adenylate kinase and the hydroxylation of acetylaldehyde by carbonic anhydrase.

Direct proton exchange between complementary nucleic acid bases.

SPECIFIC interaction between complementary nucleic acid bases, in which adenine forms strong hydrogen bonds specifically with thymine (uracil) and guanine with cytosine, is believed to be the molecular basis for the transfer of genetic information. Infrared spectroscopy and nuclear magnetic resonance have shown that such specific interaction is intrinsic to nucleic acid bases1–5. In spite of much knowledge about the static structure of the interaction6–9, little is known about the dynamic property of the base pairs. We report here quantitative evidence of direct proton exchange between complementary nucleic acid base derivatives.