Vinylsulfonylethyl derivatives of nucleic acid bases and their graft polymers on polyethyleneimine

Vinylsulfonylethyl (VSE) derivatives of the nucleic acid bases adenine, thymine, cytosine, and the nucleosides inosine and uridine have been prepared via a simple Michael reaction with divinyl sulfone. The VSE derivatives were grafted on a polyethyleneimine (PEI) backbone. PEI of different molecular weights (1400, 1800 and 50,000–100,000) were used and also two different molar ratios (1:1 and 1:2) of monomer to PEI were employed. From the ¹H-NMR and elemental analysis, it appeared that in almost all instances the grafting was quantitative. In one case, both 1-VSE-thymine and 9-VSE-adenine were grafted on the same PEI backbone. Interactions between some of these polymers were investigated by UV spectroscopy. The expected complementary base pairing was observed only in DMSO–ethylene glycol solvent system but not in DMSO. The adenine polymer showed a one-to-one interaction with the thymine polymer.     

Graft copolymers containing nucleic acid bases and L-α-amino acids

Graft copolymers of nucleic acid bases and L-α-amino acids on polyethyleneimine were synthesized, and carboxyl derivatives of adenine and thymine were grafted by the p-nitrophenyl ester method onto linear and branched polyethyleneimine. The carboxyl derivatives of nucleic acid bases were also grafted onto the monomeric graft copolymers of L -α-amino acids on polyethyleneimine; the carboxyl derivatives were obtained by the condensation of polyethyleneimine with L -α-amino acids with a coupling agent.     

Synthesis of poly(vinylamine) containing asymmetric nucleic acid base derivatives as grafted pendants

The preparations of new model polymers of polynucleotides with stereoregular poly(vinylamine) (PVAm) backbones and an optically active nucleic acid base derivative as a pending side chain are described. The grafting of (±)-, (+)-, and (?)-2-(thymin-1-yl) propionic acid to linear PVAm prepared either by hydrolysis of poly(vinyl acetamide) or poly(vinyl-t-butyl carbamate) has proven to be more difficult than the case of polyethyleneimine. This may be due to a combination of the low solubility and steric factors of PVAm. PVAm formed a complex with oximes such as ethyl-2-hydroxyimino cyanoacetate (EHICA), which activates the amino group of PVAm; it became soluble in polar solvents and gave higher percent graft. These carboxylic acid derivatives were grafted onto PVAm through amide bonds by direct coupling with sulfonic acid esters of hydroxybenzotriazoles to give optically active graft polymers. These coupling agents were found to be much superior reagents than DEPC regarding racemization. The related monomer and dimer model compounds were also prepared by the same method from 3-aminopentane and (?)-, (+)-, and meso-2,4-diaminopentane, respectively. The dimer models were separated and purified by HPLC to give models for isotactic, heterotactic, and syndiotactic polymer models. The enantiomeric purity of the optically active monomer model was determined by 360-MHz NMR spectroscopy using optically active shift reagents.     

Functional monomers and polymers. CXXXI.. Synthesis and interaction studies on polyacrylamide and polymethacrylamide derivatives containing nucleic acid bases

Acrylamide and methacrylamide derivatives of nucleic acid bases were prepared from the corresponding aminoethyl derivatives. Free-radical polymerization of these monomers in water or in organic solvents gave their polymers. From the studies of the polymer complex formation by UV spectroscopy, it was found that extremely stable polymer complexes were formed between complementary polymers containing nucleic acid bases.     

Functional monomers and polymers. LXXI. Conformation and interaction studies of poly-L-lysine derivatives with pendant nucleic acid bases

Copolymers of L -lysine and L -lysine derivatives which contained nucleic acid bases substituted on the N^ε position were synthesized by grafting nucleic acid derivatives onto poly-L -lysine. The conformation and interaction of these copolymers in solution were studied by using spectroscopic measurements. They existed in helical conformation at neutral pH values, and the polymer complex formation among them was examined by ultraviolet (UV) measurements in organic solvents. A decrease in the nucleic acid base content of the copolymers resulted in a decrease in helical structures and also in interactions with the polymer-containing complementary bases.     

The Reaction of Triplet 2-Methyl-1,4-Naphthoquinone (Menadione) with DNA and Polynucleotides

Abstract— The photoreaction of 2-methyl-l,4-naphthoquinone (MQ, menadione) with DNA and polynucleotides in argon-saturated aqueous solution (pH 7) was studied. Results from laser flash photolysis experiments indicate that triplet quinone reacts with DNA and polyA but not detectably with polyU by one-electron oxidation of the bases of the nucleic acid with formation of the radical anion of the quinone. Irradiation of argon-saturated solutions containing MQ and DNA or polynucleotides (polyU, polyA, polyG or polyC) with 334 nm light leads to an increase in molecular weight for single-stranded DNA, polyA and to a much less extent for polyU. This finding indicates crosslink formation with quantum yields in the range of 10⁻⁵-10⁻³     

Synthesis of polyesters containing nucleic acid base derivatives as pending side chains

Preparations of four diol monomers containing nucleic acid bases and the corresponding model polymers of polynucleotides with linear polyester backbone and nucleic acid base derivative as pending side chains are described. N-(1′,3′-Dihydroxy-2′-methyl-2′-propyl)-2-(thymin-l-yl)propionamide ( Ia , HMPTPA), N-(1′,3′-dihydroxy-2-methyl-2′-propyl)-2-(uracil-l-yl)propionamide ( Ib , HMPUPA), and their isomers, N-(β,β′-dihydroxyethyl)-2-(thynin-1-yl)propionamide ( IIa , HETPA) and N-(β,β′-dihydroxyethyl)-2-(uracil-1-yl)propionamide ( IIb , HEUPA) were synthesized through the selective N-acylation of 2-methyl-2-amino-1,3-propanediol and diethanolamine with 2-(thymin-1-yl)propionic acid (TPA) and 2-(uracil-1-yl)propionic acid (UPA), respectively, by the active amide-benzotriazole method. Diol monomers I and II were polycondenzed with active amide of benzotriazole such as 1,1′-(isophthaloyl)bisbenzotriazole (IPBBT) in the presence of triethylamine and in DMF at 60°C, giving polyesters containing thymine and uracil derivatives as the side group. Prior to polymer synthesis, an O-acylation of Ia using the active monoamide l-benzoylbenzotriazole was carried out as a model compound study.     

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

Free-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.     

Invite Article: The Liquid-Crystalline Phases of Double-Stranded Nucleic Acids in Vitro and in Vivo

This article describes the state of and progress in experimental studies of liquid crystals of naturally occurring nucleic acids and synthetic polynucleotides. The areas considered in this review include: (i) the liquid-crystalline phase of nucleic acids in aqueous salt solutions, (ii) the liquid-crystalline phase of nucleic acids in aqueous polymer solutions, (iii) the liquid-crystalline phase of nucleic acids in living systems. Some unsolved problems which are of interest from both a physicochemical and a biological point of view are discussed.     

Detection of Tumor Necrosis Factor Gene by Piezoelectric Nucleic Acid Sensor

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Detection of Tumor Necrosis Factor Gene by Piezoelectric Nucleic Acid Senosr

A piezoelectric nucleic acid sensor was constructed ofr detection of tumor necrosis factor gene.Two methods were employed for immobilization of nucleic acid probe on gold electrode of piezoelectric crystal.The results show that polyethyleneimine adbesion and glutaraldehyde cross-linking method has higher sensitivity,stability and selectivity than protein A method.The solid-phase nucleic acid hybridization of oligo unclecotides and tumor necrosis factor target gene sequence were monitorde using this sensor.Tumor necrosis factor gene sequence(580bp) was detected by this nucleic acid sensor for the first time.     

DyNAs: constitutional dynamic nucleic acid analogues

Dynamic cationic polymers were generated in aqueous media from functionally complementary monomers bearing nucleobase groups. (1)H NMR spectroscopy was used to follow the polycondensation reaction of the nucleobase-appended dihydrazides 1 and 2 with the dialdehydes B and C. The reversibility of these polymers was established by proton NMR spectroscopy through exchange of the dihydrazide 2 with polymer 1 B. The polymers 1 B, 2 B, 1 C, and 2 C represent dynamic biopolymers of nucleic acid type, DyNAs. Electrostatic interaction of these polymers with polyanionic entities, such as polyphosphates, polynucleotides, and polyaspartic acid, was shown to take place. It induces a change in size of the dynamic polymer, as it responds by an increase in degree of polymerization to an increase of the overall anionic charge introduced, that is, to the total electrostatic interaction.     

Monte Carlo study of three-dimensional organization of water molecules around DNA fragments

Interactions with water molecules are important for the stabilization of three-dimensional structures of nucleic acids and for their functioning. The first hydration shells of macromolecules can be considered as structural parts of nucleic acid. We performed a Monte Carlo study of systems containing a nucleic acid base or base pair with water molecules using improved potential functions. These potential functions enable experimental data on both single base–single water interaction energies and enthalpies of base hydration to be reproduced. Hydration shell structures of base pairs are dependent on the pair geometry. Structural elements of hydration shells can contribute to the pair stability and hence to the probability of mispair formation during nucleic acid biosynthesis. The distribution of water molecules around bases and base pairs is essentially nonhomogeneous.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 2002).     

The 2012 Luckhurst–Samulski Prize

Abstract

This article describes the state of and progress in experimental studies of liquid crystals of naturally occurring nucleic acids and synthetic polynucleotides. The areas considered in this review include: (i) the liquid-crystalline phase of nucleic acids in aqueous salt solutions, (ii) the liquid-crystalline phase of nucleic acids in aqueous polymer solutions, (iii) the liquid-crystalline phase of nucleic acids in living systems. Some unsolved problems which are of interest from both a physicochemical and a biological point of view are discussed.     

A novel pyrrolidinyl PNA showing high sequence specificity and preferential binding to DNA over RNA

A novel conformationally constrained pyrrolidinyl peptide nucleic acid (PNA) carrying an D-aminopyrrolidine carboxylic acid (D-Apc) spacer was synthesized, and its interactions with complementary oligo- and polynucleotides were studied by UV and CD spectroscopy. The decathymine PNA formed very stable PNA-DNA complexes with poly(dA) and (dA)(10) by a sequence-specific A-T pairing. The interaction with poly(rA) gave the corresponding PNA-RNA complex with much lower stability.     

Synthesis of diols containing nucleic acid bases and their polyesters

Preparation of four diols containing nucleic acid bases derived from 3-(thymin-1-yl)propanoic acid (3-TPA) and 3-(uracil-1-yl)propanoic acid (3-UPA), and the corresponding model polymers of polynucleotides with linear polyester backbone and nucleic acid base derivative as pendant side chains are described. N-(1′,3′-Dihydroxy-2′-methyl-2′-propyl)-3-(thymin-1-yl)propionamide ( VIa , 3-HMPTPA), N-(1′3′-dihydroxy-2′-methyl-2′-propyl)-3-(uracyl-1-yl)propionamide ( VIb , 3-HMPUPA) and their isomers, N(β,β-dihydroxyethyl)-3-(thymin-1-yl)propionamide ( VIIa , 3-HETPA), and N-(β,β-dihydroxyethyl)-3-(uracil-1-yl)propionamide ( VIIb , 3-HEUPA) were synthesized through the selective N-acylation of 2-methyl-2-amino-1,3-propanediol and diethanolamine with 3-TPA and 3-UPA, respectively, by the active ester-N-hydroxyl-1,4-epoxy-5-cyclohexene-2,3-dicarboximide (HOEC) method. The resulting diols were polycondensed with active diamide of benzotriazole (HBT) such as 1,1′-(isophthaloyl)bis-benzotriazole (IPBBT), giving polyesters containing thymine and uracil derivatives as the side group, by the selective O-acrylation of active amide-benzotriazole method.     

Synthesis of poly(vinyl alcohol) containing asymmetric nucleic acid base derivatives as grafted pendants

The preparations of new model polymers of polynucleotides with linear poly(vinyl alcohol) (PVA) backbones and an optically active nucleic acid base derivative as a pending side chain are described. (±)-, (+)-, and (?)-2-(thymin-1-yl)propionic acid were grafted onto PVA through ester bonds by direct coupling with dicyclohexylcarbodiimide (DCC) in the presence of highly active catalyst 4-pyrrolidinopyridine (PPY) to give optically active graft polymers. The corresponding monomer and dimer models have been prepared.     

Derivatization by forming Schiff bases in the study of synthetic polymers bearing amino groups by MALDI mass spectrometry

A new approach is proposed to the determination of a number of primary amino groups in polymers. It involves the formation of Schiff bases in reactions with carbonyl compounds followed by MALDI mass spectrometry study. The reaction with 2,3-dihydroxybenzaldehyde appeared to be the most efficient for polyethyleneimine derivatization. This may be due to the better co-crystallization of the matrix (2,5-dihydroxybenzoic acid, DHB) with the polymer by the imine fragment with the structure close to that of the matrix. The proposed method today is the only one for determining the number of NH₂ groups in branched polyethylenimine molecules at the molecular level.     

Comparative Study of the Radiolysis of Poly(uridylic acid) and Poly(methyluridylic acid) in Nitrous Oxide-Saturated Aqueous Solutions

A comparative study of the radiolysis of poly(uridylic acid) and poly(methyluridylic acid) in aqueous solutions saturated with N₂O was performed. The radiation-chemical yields of formation of terminal phosphate groups, intact bases, 5-hydroxy-5,6-dihydrouracil, and 5-hydroxy-5,6-dihydro-3-methyluracil and the radiation-chemical yields of decomposition of these two polynucleotides were measured. Methylation was found to inhibit almost completely the formation of terminal phosphate groups and intact bases. It was suggested that the uracil-N(3)-yl radical can be a precursor of strand breaks in poly(uridylic acid).     

PHOTOCHEMICAL REACTIONS OF THYMINE WITH CARBOXYLIC ACIDS. A MODEL FOR NUCLEIC ACID-PROTEIN PHOTOCROSSLINKING

When nucleic acid bases are UV-irradiated in the presence of carboxylic acids or carboxylate anions new photoproducts are formed as compared to the bases irradiated in the absence of carboxylic acids. The behavior of thymine and thymidine has been examined in detail. At least four photoproducts are formed in the presence of propionic acid and three in the presence of butyric acid. None of them appears to be a cyclobutyl dimer. From the concentration dependence of the rate of photoproduct formation it is concluded that the reactive excited species is the first excited singlet state of thymine. When ¹⁴C-labelled thymine is irradiated in the presence of polyglutamic acid an important part of the radioactive material is covalently linked to the polymer. Photochemical reaction of thymine with glutamic (or aspartic) acid could thus induce crosslinks between proteins and nucleic acids. It is also shown that these photoproducts are stable under usual conditions of acidic hydrolysis of UV-irradiated DNA.