Right-handed Helical Structure Research Articles

Solution Structure of Duplex DNA Containing a β-Carba-Fapy-dG Lesion

The addition of hydroxyl radicals to the C8 position of guanine can lead to the formation of a 2,6-diamino-4-hydroxy-5-formamido-2'-deoxypyrimidine (Fapy-dG) lesion, whose endogenous levels in cellular DNA rival those of 8-oxo-7,8-dihydroxy-2'-deoxyguanosine. Despite its prevalence, the structure of duplex DNA containing Fapy-dG is unknown. We have prepared an undecameric duplex containing a centrally located β-cFapy-dG residue paired to dC and determined its solution structure by high-resolution NMR spectroscopy and restrained molecular dynamic simulations. The damaged duplex adopts a right-handed helical structure with all residues in an anti conformation, forming Watson-Crick base pair alignments, and 2-deoxyribose conformations in the C2'-endo/C1'-exo range. The formamido group of Fapy rotates out of the pyrimidine plane and is present in the Z and E configurations that equilibrate with an approximate 2:1 population ratio. The two isomeric duplexes show similar lesion-induced deviations from a canonical B-from DNA conformation that are minor and limited to the central three-base-pair segment of the duplex, affecting the stacking interactions with the 5-lesion-neighboring residue. We discuss the implications of our observations for translesion synthesis during DNA replication and the recognition of Fapy-dG by DNA glycosylases.

The Structure of the XPF-ssDNA Complex Underscores the Distinct Roles of the XPF and ERCC1 Helix- Hairpin-Helix Domains in ss/ds DNA Recognition

Human XPF/ERCC1 is a structure-specific DNA endonuclease that nicks the damaged DNA strand at the 5' end during nucleotide excision repair. We determined the structure of the complex of the C-terminal domain of XPF with 10 nt ssDNA. A positively charged region within the second helix of the first HhH motif contacts the ssDNA phosphate backbone. One guanine base is flipped out of register and positioned in a pocket contacting residues from both HhH motifs of XPF. Comparison to other HhH-containing proteins indicates a one-residue deletion in the second HhH motif of XPF that has altered the hairpin conformation, thereby permitting ssDNA interactions. Previous nuclear magnetic resonance studies showed that ERCC1 in the XPF-ERCC1 heterodimer can bind dsDNA. Combining the two observations gives a model that underscores the asymmetry of the human XPF/ERCC1 heterodimer in binding at an ss/ds DNA junction.

ChemInform Abstract: Conformational Changes of Non‐B DNA

AbstractReview: 189 refs.

A new 3D supramolecular array assembled by left- and right-handed helical Ni(II) coordination polymer chains based on 3,5-dinitrobenzoate and a flexible double imidazole derivative

A new nickel(II) coordination polymer with left- and right-handed helical chains [Ni(dmbbbi)(DNBA)2(H2O)] (1) has been obtained from hydrothermal reaction of nickel(II) nitrate with a flexible double imidazole derivative 1,1-(1,4-butanediyl)bis(5,6-dimethylbenzimidazole) (dmbbbi) and 3,5-dinitrobenzoic acid (HDNBA). Single-crystal X-ray diffraction analysis reveals that the crystal is triclinic: a = 9.821(5) A, b = 13.084(5) A, c = 14.705(5) A, α = 105.249(5)°, β = 95.688(5)°, γ = 94.273(5)°, Z = 2, V = 1804.1(13) A3, ρcalc = 1.553 mg/m3, GOOF = 1.064, the final R = 0.0360 and wR = 0.0999. The crystal structure analysis indicates that the nickel atom is six coordinated by three oxygen atoms from two DNBA with two kinds of coordination modes, two nitrogen atoms from different dmbbbi and a coordination water molecule forming a [NiN2O4] subunit. The subunits are linked by dmbbbi to form a one dimensional (1D) helical coordination polymer chain and the adjacent chains are further connected by hydrogen bonding interactions to form a novel left- and right-handed helical double-chain structure. The double-chains are ultimately extended into 3D supramolecular structure through π-π stacking interactions. Moreover, thermal stability of title compound and the cyclic voltammetry behavior of compound 1 modified carbon paste electrode (1-CPE) in 1 M H2SO4 solution are investigated.

One-Dimensional Helical Homochiral Metal-Organic Framework Built from 2,2′-Dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic Acid

A homochiral metal-organic framework (MOF) based on enantiopure (R)-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic acid was synthesized. X-ray crystal diffraction studies revealed that the MOF adopts a one-dimensional infinite right-handed helical tubular structure along the a-axis, which serves as a host for the inclusion of guest dimethylformamide (DMF) molecules.

Three 2D AgI-framework isomers with helical structures controlled by the chirality of camphor-10-sulfonic acid

Three 2D Ag(I)-framework isomers were constructed from enantiopure camphor-10-sulfonic acids or racemic camphor-10-sulfonic acids, together with achiral 4-aminobenzoic acids. In complex 1, (+)-camphor-10-sulfonic acids bridge the single left-handed helices that are made up of Ag ions and 4-aminobenzoic acids, generating a homochiral 2D layer. In such a structure, the interweaving of triple left-handed homohelices was also found. It is worth noting that the helicity of complex 2 could be controlled by the handedness of the camphor-10-sulfonic acid. In complex 2, there are right-handed helical structures, including single right-handed and triple right-handed helical structures connected by (-)-camphor-10-sulfonic acids. For a comparative study, (±)-camphor-10-sulfonic acids were utilized to synthesize complex 3, in which equal numbers of right-handed or left-handed double-helical chains are created. All the complexes were characterized by single-crystal X-ray structure determination, powder X-ray diffraction, IR, TGA and element analysis. Circular dichroism spectra of complexes 1 and 2 were been studied to confirm the fact that enantiopure bridging ligands do not racemize.

Conformational changes of non-B DNA

In contrast to B-DNA that has a right-handed double helical structure with Watson-Crick base pairing under the ordinary physiological conditions, repetitive DNA sequences under certain conditions have the potential to fold into non-B DNA structures such as hairpin, triplex, cruciform, left-handed Z-form, tetraplex, A-motif, etc. Since the non-B DNA-forming sequences induce the genetic instability and consequently can cause human diseases, the molecular mechanism for their genetic instability has been extensively investigated. On the contrary, non-B DNA can be widely used for application in biotechnology because many DNA breakage hotspots are mapped in or near the sequences that have the potential to adopt non-B DNA structures. In addition, they are regarded as a fascinating material for the nanotechnology using non-B DNAs because they do not produce any toxic byproducts and are robust enough for the repetitive working cycle. This being the case, an understanding on the mechanism and dynamics of their structural changes is important. In this critical review, we describe the latest studies on the conformational dynamics of non-B DNAs, with a focus on G-quadruplex, i-motif, Z-DNA, A-motif, hairpin and triplex (189 references).

Calcium ion‐mediated assembly and function of glycosylated flagellar sheath of marine magnetotactic bacterium

Flagella of some pathogens or marine microbes are sheathed by an apparent extension of the outer cell membrane. Although flagellar sheath has been reported for almost 60 years, little is known about its function and the mechanism of its assembly. Recently, we have observed a novel type of sheath that encloses a flagellar bundle, instead of a single flagellum, in a marine magnetotactic bacterium MO-1. Here, we reported isolation and characterization of the sheath which can be described as a six-start, right-handed helical tubular structure with a diameter of about 100 nm, and a pitch of helix of about 260 nm. By proteomic, microscopic and immunolabelling analyses, we showed that the sheath of MO-1 consists of glycoprotein with an apparent molecular mass > 350 kDa. This protein, named sheath-associated protein (Sap), shows homology with bacterial adhesins and eukaryotic calcium-dependent adherent proteins (cadherin). Most importantly, we showed that calcium ions mediate the assembly of the tubular-shaped sheath and disintegration of the sheath was deleterious for smooth swimming of MO-1 cells. The disintegrated sheath was efficiently reconstituted in vitro by adding calcium ions. Altogether, these results demonstrate a novel bacterial Ca(2+) -dependent surface architecture, which is essential for bacterial swimming.

Constructions of helical coordination compounds

Helicity and chirality are essential elements of life. Many important biopolymers such as DNA and peptides possess right-handed helical structures, while the building blocks for the constructions of such biopolymers are D-ribose and L-amino acids, respectively. For better realizing the origin of the helicity of biopolymers, a tremendous expansion in research efforts has been devoted to the design of metal complexes exhibiting helical architectures in inorganic and coordination chemistry. However, to control the chirality and helicity of the entire structures at the supramolecular level is one of the major challenges in the design and synthesis of helical structures. In this highlight, we present the general approaches for the construction of helical coordination compounds, together with a few instances illustrating the correlation between the chirality of building blocks and the helicity of 1D chains, as well as the chirality transfer among the helices.

Double-Stranded Supramolecular Assembly through Salt Bridge Formation between Rigid and Flexible Amidine and Carboxylic Acid Strands

A series of monomeric strands consisting of m-terphenyl backbones with chiral rigid C-linked (3) and flexible N-linked (5) formamidines and achiral carboxylic acid (4) and flexible carboxymethyl (6) residues were synthesized, and their duplex formations through amidinium-carboxylate salt bridges were investigated by NMR, circular dichroism (CD), and UV-visible spectroscopies. The salt bridge-derived duplex formation was largely dependent on the structures of the formamidine and carboxylic acid strands, and the C-linked formamidine strand 3 formed a more stable duplex with the complementary carboxylic acid strands (4 and 6) than did the flexible N-linked formamidine strand 5. The single crystal X-ray analysis revealed that the duplex 5.4 has a skewed right-handed double helical structure. A complementary duplex dimer was also synthesized from the dimers of 5 and 4 joined by diacetylene linkers. Variable-temperature CD measurements indicated that the duplex possesses a dynamic double helical structure resulting from the flexible N-linked formamidine units.

Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA

Fragments of double-stranded DNA (dsDNA) forming a right-handed helical structure (B-DNA) stimulate cells to produce type I interferons (IFNs). While an adaptor molecule, IFN-beta promoter stimulator 1 (IPS-1), mediates dsDNA-induced cellular signaling in human cells, the underlying molecular mechanism is not fully understood. Here, we demonstrate that the extrachromosomal histone H2B mediates innate antiviral immune responses in human cells. H2B physically interacts with IPS-1 through the association with a newly identified adaptor, CIAO (COOH-terminal importin 9-related adaptor organizing histone H2B and IPS-1), to transmit the cellular signaling for dsDNA but not immunostimulatory RNA. Extrachromosomal histone H2B was biologically crucial for cell-autonomous responses to protect against multiplication of DNA viruses but not an RNA virus. Thus, the present findings provide evidence indicating that the extrachromosomal histone H2B is engaged in the signaling pathway initiated by dsDNA to trigger antiviral innate immune responses.

Fabrication of Helical Mesoporous Silica Nanostructures Using Gelators and the Mixtures with CTAC

Two chiral hydrogelators, L-18ValPyBr and D-18ValPyBr, composed of L- or D-valine, were synthesized. They self-assembled into thin membranes under high concentration and helical nanofibers under low concentration in pure water. Sol-gel transcription reactions were carried out under both acidic and basic conditions using the selfassemblies of these two gelators and the mixtures with CTAC as templates and TEOS as precursor. Under acidic conditions, minimum gel concentrations of L-18ValPyBr and D-18ValPyBr are very low. After sol-gel polymerization, a kind of cotton-like silica constructed by twisted mesoporous silica ribbons was obtained. These ribbons were 60 nm in width and 10 nm in thickness. Under basic conditions, both mesoporous twisted ribbons and nanotubes constructed by tightly coiled ribbons were obtained. Generally, left-handed helical structures were obtained by using L-18ValPyBr, while right-handed helical structures were obtained by using D-18ValPyBr. The morphologies were sensitive to the concentration of NH3. When the concentration of NH3 was 2.5 wt%, twisted ribbons were obtained. When the concentration of NH3 was higher than 5.0 wt%, nanotubes constructed by tightly coiled ribbons were obtained. Mesoporous silica structures in nano- and micro-size were prepared by using the mixtures of L-18ValPyBr and CTAC under both acidic and basic conditions. Under acidic conditions, helical mesoporous fibers were obtained, and their diameter was increased with increasing the ratio of CTAC to gelator. The nanofibers obtained under basic conditions were shorter than those obtained under acidic conditions. The mesoporous channels were parallel each other and running along the axis of nanofibers.

Polymer stabilized liquid crystal films reflecting both right- and left-circularly polarized light

A single-layer polymer stabilized liquid crystal (PSLC) film reflecting both right- and left-circularly polarized light has been developed by a wash-out/refill method. The PSLC film was achieved by prefabricating the polymer network with a left-handed helical structure and then refilling a cholesteric liquid crystal with a right-handed helical structure into the network. The reflection intensity of the PSLC film is close to 100% when the pitch lengths of the two opposite helical structures are the same. It was demonstrated that the memory effect of the polymer network is an important mechanism for the resulting film properties.

Zipped‐Up Chain‐Type Coordination Polymers: Unsymmetrical Amide‐Containing Ligands Inducing β‐Sheet or Helical Structures

The crystal structures of thirteen AgI coordination polymers involving py-CONH-(CH2)n-py (py=pyridine; n=0, 1) derivatives were determined by means of single-crystal X-ray analyses. All of the compounds form one-dimensional chains composed of AgI atoms and bridging ligands with formulas [[Ag(py-CONH-(CH2)n-py)][X]]n (X=PF6 -, ClO4 -, BF4 -, and NO3 - with solvent molecules). The unsymmetrical coordination environments around AgI atoms induce direction in the chains, that is, -[NH-(CH2)n-py-Ag-py-CO]-, which resembles the alignment of amino acid chains in proteins. In compounds [[Ag(4-pia)][X]]n (1 supersetX; 4-pia=N-(4-pyridyl)isonicotinamide; X=PF6 -, ClO4 -, BF4 -, and NO3 -), [[Ag(4-pmia)][X]]n (2 supersetX; 4-pmia=N-(pyridin-4-ylmethyl)isonicotinamide; X=PF6 -, ClO4 -H2O, and NO3 -H2O), and [[Ag(3-pmia)][X]]n (3 supersetX; 3-pmia=N-(pyridin-3-ylmethyl)isonicotinamide; X=PF6 -, ClO4 -, BF4 -, and NO3 -H2O), each chain is aligned parallel to neighboring chains, but adjacent chains run in the opposite direction. Particularly in [[Ag(3-pmia)][PF6]]n (3 supersetPF6 -), [[Ag(3-pmia)][ClO4]]n (3 supersetClO4 -), and [[Ag(3-pmia)][BF4]]n (3 supersetBF4 -), amide moieties of 3-pmia ligands are complementarily hydrogen bonded to amide moieties in neighboring chains, as in the beta-sheet motif in proteins. On the other hand, in [[Ag(4-pmna)][PF6]MeOH]n (4-pmna=N-(pyridin-4-ylmethyl)nicotinamide), all chains in the crystal form left-handed (4 a supersetPF6 -MeOH) and right-handed (4 b supersetPF6 -MeOH) helical structures with a helical pitch of 28 A. Heterogeneous anion exchanges proceed reversibly in 2, but not in 3, which provides information about the thermal stabilities of the crystals.

Assembly of a Supramolecular Architecture Based on Keggin POMs and Lanthanide Coordination Cations

Two new compounds based on Keggin polyoxometalates (POMs) [SiW12O40]4− (SiW12), [Na(H2O)3(H2L)SiW12O40](H2L)2 6H2O (1), and [Ce(H2O)3(HL)2(H2L)]2[SiW12O40]2 10H2O (2) (HL = C6H5NO2 = isonicotinic acid), have been conventionally synthesized and characterized by routine methods. Compound 1 possesses a 1D right-handed helical structure constructed by SiW12O404− {SiW12} and [Na(H2O)3(HL)] complexes. Interestingly, these right-handed helical chains are linked together via H-bonds forming a novel chiral layer. By using the similar synthesis method to that for compound 1, except for employing Ce3+ cations in instead of La3+ cations, a 3D supramolecular compound 2 based on SiW12 and Ce3+ coordination cations has been obtained, which contains 1D channels along a axis. Additionally, the luminescence properties of 2 were studied.

C3‐symmetrical self‐assembled structures investigated by vibrational circular dichroism

We demonstrate by using vibrational circular dichroism (VCD) spectroscopy that it is possible to investigate the chirality of a supramolecular polymeric system in relatively dilute solutions. Chiral C(3)-symmetrical discotic molecules, based on a trialkylbenzene-1,3,5-carboxamide, form supramolecular columnar stacks with a right-handed helical structure in solution due to intermolecular hydrogen bonds. The handedness of the supramolecular chirality is determined using electronic spectroscopy measurements. Under dilute conditions (at 10(-3) M concentrations), it was also possible to probe the hydrogen bonding moieties with IR and VCD spectroscopy on these self-assembled structures. In combination with density functional theory (DFT) calculations, we could verify the preference for a right-handed chirality in the helical stacks and the nonplanar orientation of the carbonyl groups present in the molecule. This chiral arrangement is in agreement with the structure determined for a related benzene-1,3,5-tricarboxamide by X-ray diffraction. Chirality, 2008. (c) 2008 Wiley-Liss, Inc.

Sequence-specific Solution Structures of the Four Isosequential Pairs of Single-stranded DNAs and RNAs

AbstractThe role of the sequence-context in the self-organization of four single-stranded (ss) isosequential pairs of DNAs (1 – 4) and RNAs (5 – 8), [d/r-(5'C^1^A^2^X^3^G^4^Y^5^A^6^C^7^): X^3^ = A or C, Y^5^ = A or C; sequence variations: 2^2^ = 4], has been elucidated by NMR-constrained Molecular Dynamics (MD) simulations (2 ns). Following sequence-specific observations have been made from the solution NMR and the NMR constrained MD simulation study: (i) Analysis of the NOESY footprints, mainly (H8/H6)~n~ to (H1' and H3')~n-1~ contacts, of ssDNAs (1 - 4) and ssRNAs (5 – 8) in the aqueous medium have shown that all ssDNAs (1 - 4) and ssRNAs (5 - 8) adopt right handed stacked helical structures in the NMR time scale. (ii) Intra-residual cross-peak intensities for the H(8/6)~n-~ H(1'/2'/2''/H3')~n~ contacts in ssDNAs and ssRNAs are stronger at the 3'-ends in comparison with those at the 5'-ends, suggesting that the dynamics of the nucleobases at the 3'-end are more restricted, whereas those at the 5'-end are more flexible. (iii) This relative NMR found mobility is consistent with the final RMSd calculations of the final NMR-MD structures of ssDNAs and ssRNAs. They show that the 5'-end nucleobases have higher RMSd values compared to those at the 3'-end, except for the sequence d/r(5'C^1^A^2^A^3^G^4^A^5^A^6^C^7^). (iv) Relative nOe intensities of inter-residual H(8/6)~n~ - H(1')~n-1~ and H(8/6)~n~ - H(3')~n-1~ contacts, as well as NMR observed fluctuations in the sugar conformations, for ssDNAs (1 – 4) and ssRNAs (5 – 8) show that no ssDNA or ssRNA adopts either a typical B-type DNA or A-type RNA form. (v) In the final NMR-MD structures all the [H8/6N~(n)~ — H1'N~(n-1)~/ H3'N~(n-1)~, N = A, G, C] distances in different isosequential pairs of ssDNA (1 – 4) and ssRNA (5 – 8) change depending upon the sequence context of the single-stranded nucleic acids. Both in the deoxy and ribo series, it is the purine-rich sequences [d/r-(5'C^1^A^2^A^3^G^4^A^5^A^6^C^7^) which form the most stable self-organized right-handed helical structures because of the favorable purine-purine stacking interactions. (vi) Stacking pattern at each of the dinucleotide steps show that the base-base nearest neighbor stacking interactions depend solely upon the sequence contexts of the respective ssDNAs (1 – 4) and ssRNAs (5 – 8). See pages 47 – 145 for Supplementary Information for detailed spectroscopic data.

Nanotweezers for Chiral Discrimination of Carbon Nanotubes

A single-walled carbon nanotube (SWCNT) may have a left- or right-handed helical structure (designated M and P by IUPAC nomenclature), in accord with the graphene sheet from which the nanotube was formed. To extend the potential applications and fundamental studies of carbon nanotubes, a method for separating the P and M forms is desired. Chiral bisporphyrins 1 and 2 selectively complex with either (P)- or (M)-SWCNTs and thereby enable preferential extraction of one chiral form.

Improved Optical Enrichment of SWNTs through Extraction with Chiral Nanotweezers of 2,6-Pyridylene-Bridged Diporphyrins

Chiral single-walled carbon nanotubes (SWNTs) have left- and right-handed helical structures (M and P, respectively, according to the IUPAC nomenclature). In this report, optically active SWNTs were obtained through preferential extraction of (M)- or (P)-SWNTs with 2,6-pyridylene-bridged chiral diporphyrins 1. In the circular dichroism (CD) spectra, the SWNTs extracted with 1 exhibit much larger intensity than those extracted with 1,3-phenylene-bridged chiral diporphyrins 2, indicating an improved chiral discrimination ability of 1. In particular, (6,5)-SWNTs display the most intensified CD signals among the SWNTs extracted with 1. In addition, the SWNT extraction ability of 1 has been shown to be considerably enhanced in comparison to 2. These improved discrimination and extraction abilities of 1 are attributed to the formation of its more stable SWNT complex. Computer-calculated energy minimized structures for 1:(6,5)-SWNT complexes show that (R)- and (S)-1 form complexes preferentially with (M)- and (P)-(6,5)-SWNTs, respectively. These calculations also predict that the 1:(6,5)-SWNT complex is approximately 1.6 kcal mol-1 more stable than the corresponding complex of 2, accounting for the improved abilities of 1 in the chiral discrimination and extraction.

Molecular Modeling of Conformational Properties of Oligodepsipeptides

A depsipeptide is a chemical structure consisting of both ester and amide bonds. Quantum mechanics calculations have been performed to investigate the conformational properties of a depsidipeptide in the gas and solution phases. Similar to an alanine dipeptide, the depsidipeptide exhibits a strong preference for the polyproline II (PPII) helical conformation. Meanwhile, due to the changes in the intramolecular interaction, the propensity for beta-sheets and alpha-helices diminishes while an unusual inclination for the (phi,psi) = (-150 degrees ,0 degrees ) conformation was observed. A molecular mechanics model has been developed for polydepsipeptides based on the quantum mechanical study. Both simulated annealing and replica exchange molecular dynamics simulations have been carried out on oligodepsipeptide sequences with alternating depsi and natural residues in solution. Novel helical structures have been indicated from the simulations. When glycine is used as the alternating natural amino acid residue, the PPII conformation of a depsi residue stabilizes the peptide into a right-handed helical structure while the alpha-helical conformation of the depsi residue favors an overall left-handed helical structure. The free energy analysis indicates that both the left- and the right-handed helices are equally likely to exist. When charged lysine is introduced as the alternating natural residue, however, it is found that the depsipeptide sequence prefers an extended conformation as in PPII. Our results indicate that the depsipeptide is potentially useful in designing protein mimetics with controllable structure, function, and chemistry.