Triostin A Derived Cyclopeptide as Architectural Template for the Alignment of Four Recognition Units

The DNA bisintercalator triostin A is structurally based on a disulfide-bridged depsipeptide scaffold that provides preorganization of two quinoxaline units in 10.5 Å distance. Triostin A analogues are synthesized with nucleobase recognition units replacing the quinoxalines and containing two additional recognition units in between. Thus, four nucleobase recognition units are organized on a rigid template, well suited for DNA double strand interactions. The new tetra-nucleobase binders are synthesized as aza-TANDEM derivatives lacking the N-methylation of triostin A and based on a cyclopeptide backbone. Synthesis of two tetra-nucleobase aza-TANDEM derivatives is established, DNA interaction analyzed by microscale thermophoresis, cytotoxic activity studied and a nucleobase sequence dependent self-aggregation investigated by mass spectrometry.     

Purine 3′:5′‐cyclic nucleotides with the nucleobase in a syn orientation: cAMP,cGMP and cIMP

Purine 3′:5′‐cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid‐state conformational details still require investigation. Five crystals containing purine 3′:5′‐cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3′:5′‐cyclic phosphate dihydrate, C₁₀H₁₂N₅O₆P·2H₂O or cAMP·2H₂O, (I), adenosine 3′:5′‐cyclic phosphate 0.3‐hydrate, C₁₀H₁₂N₅O₆P·0.3H₂O or cAMP·0.3H₂O, (II), guanosine 3′:5′‐cyclic phosphate pentahydrate, C₁₀H₁₂N₅O₇P·5H₂O or cGMP·5H₂O, (III), sodium guanosine 3′:5′‐cyclic phosphate tetrahydrate, Na⁺·C₁₀H₁₁N₅O₇P⁻·4H₂O or Na(cGMP)·4H₂O, (IV), and sodium inosine 3′:5′‐cyclic phosphate tetrahydrate, Na⁺·C₁₀H₁₀N₄O₇P⁻·4H₂O or Na(cIMP)·4H₂O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP⁻ in (IV) and cIMP⁻ in (V)] are syn conformers about the N‐glycosidic bond, and this nucleobase arrangement is accompanied by C_rib—H…N_pur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn–anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter‐nucleotide contacts in (I)–(V) have been systematized in terms of the chemical groups involved. All five structures display three‐dimensional hydrogen‐bonded networks.     

核酸碱基桥连配体对金属-生物分子框架配合物(MBioFs)的形貌与吸收性质的影响

合成了一系列金属-生物分子框架配合物,核酸碱基作为连接分子决定了其多样的微观结构及不同的吸收性质。     

Post-synthetic modification of oligonucleotides containing 5-trifluoromethylpyrimidine bases

A practical and operationally simple post-synthetic modification of oligonucleotides containing 5-trifluoromethylpyrimidine bases is described. Trifluoromethyl group was used as a post-synthetic precursor and 5-trifluoromethylpyrimidine bases within oligonucleotides were converted into the corresponding 5-carboxy-, 5-cyano-, 5-amidinyl-, and 5-carbamoyl derivatives by treatment with an alkaline solution and amines. Moreover, post-synthetic treatment of fully protected and controlled pore glass (CPG)-attached oligonucleotides proceeded successfully with the simultaneous removal of all protecting groups, cleavage from CPG, and conversion of the trifluoromethyl group to afford the corresponding modified oligonucleotides.     

Melamine driven supramolecular self‐assembly of nucleobase derivatives in water

Water‐soluble supramolecular polymers, especially made up of biomolecules, are ideally suited to build new biomaterials that can mimic or interact with dynamic, biological environments. Here, two derivatives from thymine (T), that is N‐[2‐(3,4‐Dihydro‐5‐methyl‐2,4‐dioxo‐1(2H)‐pyrimidinyl)acetyl]‐L‐phenylalanine (T‐phe) and N‐(2‐Aminoethyl)‐3,4‐dihydro‐5‐methyl‐2,4‐dioxo‐1(2H)‐pyrimidineacetamide (T‐NH₂) were synthesized. Then the optimal condition for self‐assembly of T‐phe and T‐NH₂ driven by melamine (M) was explored. It was observed that M/T kept at 1:3 with equivalent T‐phe and T‐NH₂ under neutral environment resulted in long fibers (>1 μm) with extremely high aspect ratios, which suggested that electrostatic and π‐stacking interactions could be effectively orchestrated by hydrogen bonds to direct the hierarchical assembly. Furthermore, hydrogels were spontaneously generated with a concentrated solution of T‐phe, T‐NH₂, and M due to the fibril entanglement. Given its biomimetic nature and efficient self‐assembly process, this newly developed supramolecular polymer stacked by tetrameric structures represented an innovative concept and pathway for novel bio‐inspired materials. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 789–796     

The Use of Voltammetry for Sorption Studies of Arsenic (III) Ions by Magnetic Beads Functionalized with Nucleobase Hydrazide Derivatives

In this work the interaction characteristics of nucleobases with As(III) are studied. Novel materials consisting of magnetic nanoparticles (MNPs) functionalized with adenine hydrazide (AH), guanine hydrazide (GH) and uracil hydrazide (UH) were elaborated. The adsorption isotherms were investigated electrochemically and it was shown that the adsorption capacity of the nanoparticles towards arsenic (III) increased in the following order: AH<UH<GH. The electrochemical detection of As(III) using the GH functionalized MNPs offered better results compared with the other functionalizations, with a sensitivity of 1.92 μA μg⁻¹ L and a limit of detection of 1.6 μg/L (21 nM).     

Stabilizing or destabilizing oligodeoxynucleotide duplexes containing single 2'-deoxyuridine residues with 5-alkynyl substituents

The 5-position of pyrimidines in DNA duplexes offers a site for introducing alkynyl substituents that protrude into the major groove and thus do not sterically interfere with helix formation. Substituents introduced at the 5-position of the deoxyuridine residue of dU:dA base pairs may stabilize duplexes and reinforce helices weakened by a low G/C content, which would otherwise lead to false negative results in DNA chip experiments. Here we report on a method for preparing oligonucleotides with a 5-alkynyl substituent at a 2'-deoxyuridine residue by on-support Sonogashira coupling involving the fully assembled oligonucleotide. A total of 25 oligonucleotides with 5-alkynyl substituents were prepared. The substituents either decrease the UV melting point of the duplex with the complementary strand or increase it by up to 7.1 degrees C, compared with that of the unmodified control duplex. The most duplex-stabilizing substituent, a pyrenylbutyramidopropyne moiety, is likely to intercalate but does not prevent sequence-specific base pairing of the modified deoxyuridine residue or the neighboring nucleotides. It also increases the signal for a target strand when employed on a small oligonucleotide microarray. The ability to tune the melting point of a DNA dodecamer duplex with a single side chain over a temperature range of >11 degrees C may prove useful when developing DNA sequences for biomedical applications.     

On Mixed-Valence Dinuclear PtII,PtIII Nucleobase Complexes Derived from cis-Diamineplatinum(II): Effect of steric bulk of amine ligands on the Pt-oxidation state

A series of closely related dinuclear (head-head) Pt^II complexes of general composition cis-[a₂PtL₂Pta′₂]²⁺ with a,a′ = NH₃ or CH₃NH₂ and L = 1-methyluracilate-N3,O4 (1-MeU) or 1-methylthyminate-N3,O4 (1-MeT) has been prepared and the solution behavior toward Ce^IV oxidation studied. The X-ray crystal structure of a representative example cis-[(CH₃NH₂)₂Pt(1-MeU)₂Pt(CH₃NH₂)₂](ClO₄)₂ · 0.5 H₂O ( 1b ), has been determined: Monoclinic, space group P2₁/c, a = 11.907(7) Å, b = 19.087(14) Å, c = 12.525(7) Å, β = 90.49(4)°, Z = 4. Oxidation of these diplatinum(II) complexes ([Pt^2.0]₂) with Ce^IV in aqueous solution to the corresponding diplatinum(III) species ([Pt^3.0]₂) proceeds via tetranuclear [Pt^2.25]₄ or dinuclear [Pt^2.5]₂ mixed-valence state compounds, depending on the nature of the a′ ligands: with a′ = NH₃, blue green [Pt^2.25]₄ forms, whereas with a′ = CH₃NH₂, purple [Pt^2.5]₂ represents the intermediate. This difference is interpreted in terms of differences in bulk between NH₃ and CH₃NH₂ ligands trans to the O(4) positions of the bridging nucleobases which influence the ability of dinuclear species to associate via the O(4)₂ Pt a₂′ faces.     

Hemicyanine-linked pyrimidine mimics as solvatochromic fluorophores with visible excitation wavelengths

The design of solvatochromic fluorescent nucleosides with visible excitation wavelengths is a goal towards the generation of modified oligonucleotides for fluorimetry-based molecular imaging. Herein, two hemicyanine-linked C5-2′-deoxyuridine nucleosides (PyI-dU and APPy-dU) have been synthesized by first generating hemicyanine-alkyne precursors that were attached via the alkyne moiety to 5-iodo-2′-deoxyuridine (5-I-dU) by Sonogashira coupling. The photophysical properties of the hemicyanine-linked dU probes have been characterized and compared to the corresponding properties of the hemicyanine-alkyne precursors. The nucleoside probe PyI-dU exhibits optical features that mimic the properties of the free hemicyanine-alkyne precursor, while the APPy-dU probe displays more favorable optical properties (longer excitation wavelength, brighter emission in water) than its precursor that is ascribed to π-stacking interactions between the hemicyanine dye with the dU nucleobase. Overall, probe APPy-dU is a superior solvatochromic fluorophore than PyI-dU suggesting its greater utility for fluorescent imaging applications.     

Nucleobase-induced supramolecular polymerization in the solid state

Supramolecular polymerization, that is, the self-assembly of polymer-like materials through the utilization of the noncovalent bond, has been a developing area of research over the last decade. In this article, we report the synthesis of nucleobase-terminated (N⁶-anisoyl-adenine and thymine) low-molecular-weight poly(tetrahydrofuran) macromonomers (<2000 g mol⁻¹). The adenine-derived supramolecular telechelic polymer self-assembled in the solid state to yield materials with film- and fiber-forming capabilities. This material was thermally reversible and exhibited a ceiling temperature, above which a drop in viscosity was observed and fibers could no longer be obtained. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3589–3596, 2003