Structural and biochemical impact of C8-aryl-guanine adducts within the NarI recognition DNA sequence: influence of aryl ring size on targeted and semi-targeted mutagenicity

Chemical mutagens with an aromatic ring system may be enzymatically transformed to afford aryl radical species that preferentially react at the C8-site of 2′-deoxyguanosine (dG). The resulting carbon-linked C8-aryl-dG adduct possesses altered biophysical and genetic coding properties compared to the precursor nucleoside. Described herein are structural and in vitro mutagenicity studies of a series of fluorescent C8-aryl-dG analogues that differ in aryl ring size and are representative of authentic DNA adducts. These structural mimics have been inserted into a hotspot sequence for frameshift mutations, namely, the reiterated G3-position of the NarI sequence within 12mer (NarI(12)) and 22mer (NarI(22)) oligonucleotides. In the NarI(12) duplexes, the C8-aryl-dG adducts display a preference for adopting an anti-conformation opposite C, despite the strong syn preference of the free nucleoside. Using the NarI(22) sequence as a template for DNA synthesis in vitro, mutagenicity of the C8-aryl-dG adducts was assayed with representative high-fidelity replicative versus lesion bypass Y-family DNA polymerases, namely, Escherichia coli pol I Klenow fragment exo− (Kf−) and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Our experiments provide a basis for a model involving a two-base slippage and subsequent realignment process to relate the miscoding properties of C-linked C8-aryl-dG adducts with their chemical structure

Structural and biochemical impact of C8-aryl-guanine adducts within the Narl recognition DNA sequence: influence of aryl ring size on targeted and semi-targeted mutagenicity

Sherpa Romeo green journal, open accessChemical mutagens with an aromatic ring system may be enzymatically transformed to afford aryl radical species that preferentially react at the C8-site of 2 -deoxyguanosine (dG). The resulting carbonlinked C8-aryl-dG adduct possesses altered biophysical and genetic coding properties compared to the precursor nucleoside. Described herein are structural and in vitro mutagenicity studies of a series of fluorescent C8-aryl-dG analogues that differ in aryl ring size and are representative of authentic DNA adducts. These structural mimics have been inserted into a hotspot sequence for frameshift mutations, namely, the reiterated G3-position of the NarI sequence within 12mer (NarI(12)) and 22mer (NarI(22)) oligonucleotides. In the NarI(12) duplexes, the C8- aryl-dG adducts display a preference for adopting an anti-conformation opposite C, despite the strong syn preference of the free nucleoside. Using the NarI(22) sequence as a template for DNA synthesis in vitro, mutagenicity of the C8-aryl-dG adducts was assayed with representative high-fidelity replicative versus lesion bypass Y-family DNA polymerases, namely, Escherichia coli pol I Klenow fragment exo− (Kf−) and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Our experiments provide a basis for a model involving a two-base slippage and subsequent realignment process to relate the miscoding properties of C-linked C8-aryl-dG adducts with their chemical structures.Ye

Novel 4-vinylpyridine-extended metal-dibenzoylmethanate host frameworks : structure, polymorphism, and inclusion properties

In this contribution we show that host materials based on metal dibenzoylmethanates (DBM) can be extended in a versatile way by decreasing the packing efficiency of the simpler metal DBM's reported earlier. Specifically, this can be accomplished by coordinating two 4-vinylpyridines (4-ViPy) to the metal (Ni or Co) DBM units to give [M(4-ViPy)2(DBM)2] host complexes. These display a remarkable polymorphism and an ability to form inclusion compounds with a large variety of organic species. Five non-clathrate phases representing three polymorphic types and twenty-eight inclusion compounds with nineteen guests representing five structural types were isolated and studied in varying degrees of detail. The inclusion compounds can be prepared by recrystallization or by interaction of the solid host with guest vapor. In the latter case, the process realization, kinetics and final product strongly depend on the host polymorph chosen as starting material. Kinetic studies executed with powder XRD suggest that transient formation of inclusion compounds may occur even during solvent vapor induced transformation of one guest-free polymorph to another. The beta polymorph of the Ni-host reveals the strongest clathratogenic ability as well as a high selectivity towards certain homologues and isomers. Its properties give insight into the concept of ldquoflexible zeolite mimicsrdquo, or ldquoapohostsrdquo, as this empty host form is energetically and structurally predisposed towards inclusion processes. In all eleven (three host and eight clathrate) structures studied by single crystal X-ray diffraction the [M(4-ViPy)2(DBM)2] complex molecule is trans-configured. In most, the host molecules show effective packing in one dimension by forming parallel chains. Guest species are located between the chains in cages or channels formed by combining voids in the host molecules belonging to adjacent chains. The corresponding Ni and Co versions of the compounds studied were similar.NRC publication: Ye

4-vinylpyridine-modified nickel and cobalt dibenzoylmethanates as new hosts

NRC publication: Ye

Dipeptides as microporous mMaterials

Robust porous frameworks are formed by the dipeptides L-Ala-L-Val (see structure) and L-Val-L-Ala that have a high capacity and selectivity for gas sorption. The dipeptides assemble through hydrogen bonds as a 6\u2081 helix to form channels with average diameters of 5.13 and 4.90 \uc5, respectively.NRC publication: Ye

Micropores in crystalline dipeptides as seen from the crystal structure, He pycnometry, and \ub9\ub2\u2079Xe NMR Spectroscopy

Eight crystalline dipeptides were studied: AV (Ala-Val), VA (Val-Ala), AI (Ala-Ile), VV (Val-Val), IA (Ile-Ala), IV (Ile-Val), VI (Val-Ile), and LS (Leu-Ser) (all LL isomers). The first seven form an isostructural series (space group P6\u2081), whereas LS has a different structure (P6\u2085). All structures display H-bonded tubular assemblies of the dipeptide molecules resulting in open ultramicropores in the form of isolated one-dimensional (1D) channels. The total porosity of the materials ranges from 4 to 12% (micropore volume from 0.04 to 0.12 cm\ub3/g). Calculations based on the crystal structures, He pycnometry, and solid-state \ub9\ub2\u2079Xe NMR methods were used to obtain a comprehensive description of the geometry and properties of the micropores. The following order was established for the channel diameter: AV > VA > AI > VV > IA > IV > VI, with >5 \uc5 for AV and <4 \uc5 for VI; LS is close to AI. The observed sorption behavior cannot be described adequately based on the crystal structure and can only be understood if one takes into account the dynamics of the host matrix. The pores are chiral, with the center of the channel describing a right-handed helix (left-handed for LS). The following order was established for the channel helicity: VA > IA > IV > AV 48 AI 48 VV > VI > LS, with a helix diameter of ~2 \uc5 for VA, IA, and IV and ~1 \uc5 or less for the remaining dipeptides. A comparison of the dipeptides studied with other supramolecular materials is given and the potential for applications is discussed.NRC publication: Ye

The ability of lower peptides to form co-crystals: inclusion compounds of Leu-Leu-Leu tripeptide with pyridine and picolines

Co-crystals of L-leucyl-L-leucyl-L-leucine tripeptide (LLL) with pyridine (Py), \u3b1-picoline (2-MePy), \u3b2-picoline (3-MePy) and \u3b3-picoline (4-MePy) have been prepared and studied. Single-crystal XRD analyses reveal the following formulas: LLL*(Py) (1), LLL*(2-MePy)*0.12(H2O) (2), LLL*(3-MePy) (3), and LLL*(4-MePy)*0.14(H2O) (4). The compounds may be described as inclusion compounds of LLL (host), pyridine or picolines (guest) and water (secondary guest). The host LLL molecules are arranged in anti-parallel \u3b2-sheet layers and have conformations consistent with this type of peptide organization. The layers are packed by van der Waals forces with an interlayer distance of 11.5\u201311.8 \uc5. The isobutyl side groups of leucyl residues protrude into the interlayer space and form large channels on one side of the layer. The guest molecules reside in the channels and form H-bonds to the host NH3+ groups. The crystal structures have two host molecules in the asymmetric unit, which in most cases, exhibit rarely observed whole-molecule disorder. Three of the compounds invariably form as twinned crystals. TGA measurements of bulk products reveal the following compositions: LLL*1.04(Py) (1), LLL*0.99(2-MePy) (2), LLL*0.96(3-MePy) (3), and LLL*0.92(4-MePy) (4), in good agreement with the XRD results. The character of thermal dissociation implies the preservation of the host layered structure as guest molecules diffuse out of the channels. Compound 2 dissociates with the formation of an intermediate with the stoichiometry of LLL*0.5(2-MePy).NRC publication: Ye

Ferromagnetic superexchange in a 1D -[LaIII-radical]- coordination polymer

The first coordination polymer of a bridging radical 1,2,3,5-dithiadiazolyl ligand is reported. Upon coordination with the La(hfac)3 fragment, the paramagnetic 4-(benzoxazol-20-yl)-1,2,3,5-dithiadiazolyl (boaDTDA) ligand forms a one-dimensional (1D) alternating -[La(hfac)3- boaDTDA]n- polymer exhibiting ferromagnetic (FM) coupling between the radicals, mediated through the diamagnetic LaIII ion (hfac = 1,1,1,5,5,5-hexafluoroacetylacetonato)