Characterization and elucidation of coordination requirements of adenine nucleotides complexes with Fe(II) ions

In spite of the significant role of iron ions-nucleotide complexes in living cells, these complexes have been studied only to a limited extent. Therefore, we fully characterized the ATP:Fe(II) complex including stoichiometry, geometry, stability constants, and dependence of Fe(II)-coordination on pH. A 1:1 stoichiometry was established for the ATP:Fe(II) complex based on volumetric titrations, UV and SEM/EDX measurements. The coordination sites of ferrous ions in the complex with ATP, established by 1H-, 31P-, and 15N-NMR, involve the adenine N7 as well as P(alpha), P(beta), and P(gamma). Coordination sites remain the same within the pH range of 3.1-8.3. By applying fluorescence monitored Fe(II)-titration, we established a logK value of 5.13 for the Fe(ATP)2- complex, and 2.31 for the Fe(HATP)-complex. Ferrous complexes of ADP3- and AMP2- were less stable (log K 4.43 and 1.68, respectively). The proposed major structure for the Fe(ATP)2- complex is the 'open' structure. In the minor 'closed' structure N7 nitrogen is probably coordinated with Fe(II) through a bridging water molecule. The electronic and stereochemical requirements for Fe(II)-coordination with ATP4- were probed using a series of modified-phosphate or modified-adenine ATP analogues. We concluded that: Fe(II) coordinates solely with the phosphate-oxygen atom, and not with sulfur, amine, or borane in the cases of phosphate-modified analogues of ATP; a high electron density on N7 and an anti conformation of the adenine-nucleotide are required for enhanced stability of ATP analogues:Fe(II) complexes as compared to ATP complexes (up to more than 100-fold); there are no stereochemical preferences for Fe(II)-coordination with either Rp or Sp isomers of ATP-alpha-S or ATP-alpha-BH3 analogues.     

INHIBITION OF SOME HEPATIC GLYCOSIDASES BY THE DISECO NUCLEOSIDE, 4-AMINO-3-(D-GLUCOPENTITOL-1-YL)- 5-MERCAPTO-1,2,4-TRIAZOLE AND ITS 3-METHYL ANALOG

ABSTRACT

The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-l-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on α- and β-glucosidases, β-glucuronidase as well as α-amylase have been investigated. α-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for α-glucosidase. Moreover, they exert a relatively potent inhibition on α-glucosidase with a K_i magnitude of 3.6×10^?4, 9.5×10^{? 5} M.     

Synthesis of enantiomeric pureCis-dichloroplatinum(II) amino acid complexes

The reaction of potassium tetrachloroplatinate(II) with six representative sulfurcontaining amino acids, namely,d- andl-cysteine,d- andl-methionine and its methyl ester hydrochloride gives the corresponding enantiomerically purecis-dichloroplatinum(II) complexes. This represents the first reported series of well-characterized enantiomerically pure platinum(II) complexes for bothd- andl-amino acids. The spectroscopic properties, including IR,¹H-NMR, and¹³C NMR, of these complexes and their configuration are discussed.     

Isosteric Phosphonate Pyrrolidine-Based Dinucleoside Monophosphate Analogues

Abstract

A novel α- and β-configured pyrrolidine nucleoside phosphonates in adenine series were synthesized from trans-4-hydroxy-L-proline as starting material. d(ApA) analogues were also prepared and studied with respect to their hybridization properties with polyU.     

WDNM1 is Associated with Differentiation and Apoptosis of Mammary Epithelial Cells

In this study, we show that expression of the Westmead DMBA8 nonmetastatic cDNA 1 (WDNM1) gene was increased upon SFM and/or TNFα treatment, with a corresponding increase in apoptotic cells, and gradually decreased following re-stimulation with serum in HC11 mammary epithelial cells. TNFα induced WDNM1 expression showed the NFκB-dependent mechanism since it's expression was abrogated in IκBαM (super-repressor of NFκB)-transfected cells, but not those transfected with control vector. Furthermore, overexpression of WDNM1 suppressed growth and differentiation, and accelerated apoptosis of HC11 cells. Thus, our results demonstrate that WDNM1 gene expression, regulated by the TNFα-NFκB signal pathway, is associated with HC11 cell apoptosis.     

DNA binding,photocleavage, antimicrobial and cytotoxic properties of Ru(II) polypyridyl complexes containing BOPIP ligand, (BOPIP = {2-(4-(benzyloxy) phenyl)-1H-imidazo [4,5-f] [1,2]phenanthroline})

A novel ligand BOPIP (BOPIP?=?{2-(4-(benzyloxy)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}) and its mononuclear Ru(II) polypyridyl complexes [Ru(phen)₂ BOPIP]²⁺(1) (phen?=?1,10-Phenanthrolene), [Ru(bpy)₂ BOPIP]²⁺(2) (bpy?=?2,2′ bipyridyl), [Ru(dmb)₂ BOPIP]²⁺(3) (dmb?=?4, 4′ -dimethyl 2, 2′ -bipyridine), [Ru(Hdpa)₂ BOPIP]²⁺(4) (Hdpa?=?2,2′dipyridylamine) have been synthesized successfully and characterized by elemental analysis, UV-vis, IR, ¹H, ¹³ Gill, M. R.; Garcia-Lara, J.; Foster, S. J.; Smythe, C.; Battaglia, G.; Thomas, J. A. A Ruthenium(II) polypyridyl Complex for Direct Imaging of DNA Structure in Living Cells. Nat. Chem. 2009, 1, 662–667.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]C-NMR, and ESI-MS Spectroscopy. The interaction of these complexes with CT-DNA was studied using absorption, emission techniques, viscosity measurements and molecular docking studies. The docking study also supports the binding ability of complexes obtained through the absorption and emission techniques. These studies reveal that the Four Ru(II) polypyridyl complexes bind to DNA predominantly by intercalation. The Antimicrobial activity and cytotoxicity of these complexes are also reported.     

Association Between PCR-SSCP of Bone Morphogenetic Protein 15 Gene and Prolificacy in Jining Grey Goats

The Jining Grey is a prolific local goat breed in P.R. China. Bone morphogenetic protein 15 (BMP15) gene that controls high fecundity of Inverdale, Hanna, Lacaune, Belclare, Cambridge, and Small Tailed Han ewes was studied as a candidate gene for the prolificacy of Jining Grey goats. According to the sequence of ovine BMP15 gene, six pairs of primers were designed to detect single nucleotide polymorphisms in exon 1 and exon 2 of the BMP15 gene in both high fecundity breed (Jining Grey goats) and low fecundity breeds (Boer, Liaoning Cashmere, and Inner Mongolia Cashmere goats) by single strand conformation polymorphism (SSCP). Two pairs of primers (F1/R1 and F2/R2) were used to amplify the exon 1. Four pairs of primers (F3/R3, F4/R4, F5/R5, and F6/R6) were used to amplify the exon 2. Only the products amplified by primer F5/R5 displayed polymorphism. Results indicated that two genotypes (AA and AB) were detected in prolific Jining Grey goats and only one genotype (AA) was detected in low fecundity goat breeds. In Jining Grey goats frequencies of genotypes AA and AB were 0.10 and 0.90, respectively. Sequencing revealed two point mutations (G963A and G1050C) of BMP15 gene in the AB genotype in comparison to the AA genotype. In Jining Grey goats the heterozygous AB does had 1.13 (p < 0.01) kids more than the homozygous AA does. These results preliminarily showed that the BMP15 gene is either a major gene that influences the prolificacy of Jining Grey goats or a molecular genetic marker in close linkage with such a gene.     

Synthesis and Biological Evaluation of Some 5-Nitro- and 5-Amino Derivatives of 2′-Deoxycytidine, 2′,3′-Dideoxyuridine,and 2′,3′-Dideoxycytidine

Abstract

In this article, we describe the synthesis of 5-nitro-1-(2-deoxy-α-D-erythro-pentofuranosyl)cytosine (4α), 5-nitro-1-(2-deoxy-β-D-erythro-pentofuranosyl)cytosine (4β), 5-amino-1-(2-deoxy-α-D-erythro-pentofuranosyl)cytosine (5α), 5-nitro-1- (2-deoxy-β-D-erythro-pentofuranosyl)cytosine (5β), 5-nitro-1-(2,3-dideoxy-β- D-ribofuranosyl)uracil (6β), 5-amino-1-(2,3-dideoxy-α,β-D-ribofuranosyl)uracil (7), 5-nitro-1-(2,3-dideoxy-α,β-D-ribofuranosyl)cytosine (8) and 5-amino-1-(2,3-dideoxy-β-D-ribofuranosyl)cytosine (9β). The prepared compounds were tested for their activity against HIV and HBV viruses, but they did not show significant activity.     

Oligonucleotides Containing Disaccharide Nucleosides: Synthesis,Physicochemical, and Substrate Properties

Abstract

The efficient synthesis of oligonucleotides containing 2′-O-β-D-ribofuranosyl (and β-D-ribopyranosyl)nucleosides, 2′-O-α-D-arabinofuranosyl (and α-L-arabinofuranosyl)nucleosides, 2′-O-β-D-erythrofuranosylnucleosides, and 2′-O-(5′-amino-5-deoxy-β-D-ribofuranosyl)nucleosides have been developed.     

Comparative Messenger RNA Expression of FSHβ, LHβ, FSHR,LHR, and ERβ in High and Low Prolific Goat Breeds

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have a central role in follicle growth and maturation, but no clear differences between breeds with different ovulation rates have been found. Therefore, this study investigated mRNA expression of FSHβ, LHβ, FSH receptor (FSHR), LH receptor (LHR), and estrogen receptor-β (ERβ) genes in prolific Lezhi black (LB) goats and nonprolific Tibetan (TB) goats by real-time PCR. Follicles and pituitaries were recovered from goats at 12–24 h after onset of estrus. Real-time PCR analysis revealed that the expression levels of FSHβ and LHβ mRNA were significantly higher (p < 0.01) in pituitary of LB than in TB does, but the expression levels of FSHR and LHR mRNA in follicle of TB were greater (p < 0.05). Expression level of follicular ERβ was not different between the two breeds. Data provide evidence that the greater ovulation rate in the LB goat as compared to the TB breed is associated with a greater gonadotropin expression during follicular phase.     

Bioavailability and speciation of arsenic in urban street dusts from Baoding city,China

Twenty-one street dust samples were collected from the urban sites in Baoding, China, to investigate the species and bioavailabilty of arsenic in them. The ecological risk and bioavailability of arsenic were evaluated using three models including Bioavailability Factor (BF), Contamination Factors (C_f)and Geoaccumulation Index model (I_geo). The species of arsenic in the dust samples were analyzed using an optimized BCR sequential extraction method. The total concentrations of As in the street dust samples ranged from 13.16 mg kg^?1 to 67.26 mg kg^?1. Geoaccumulation index (I_geo) of As ranged from 0.28 to 1.99. The speciation analysis indicated that As in the street dust samples were mainly in the residual fraction (F4), and the proportion ranged from 84.35% to 87.07%. Moreover, the ranges of the BF and C_f were 0.650–0.129 and 0.119–0.186, respectively. The results indicated that arsenic contained in the street dust samples was with low bioavailability.     

A Facile Synthetic Method for 3′-α-Fluoro- 2′,3′-dideoxyadenosine

Abstract

A facile method for the synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine (5) has been developed using a novel rearrangement of 3′-β-bromine to the 2′-β position during 3′-α fluorination.     

Recent Advances in the Synthesis of Conformationally Locked Nucleosides and Their Success in Probing the Critical Question of Conformational Preferences by Their Biological Targets

Abstract

The present work describes some recent approaches to the syntheses of three classes of locked-North nucleosides: β -D-ribo-, β-D-deoxyribo-, and β-D-dideoxyribonucleosides. The method developed for the latter class permitted access to a novel bicyclo[3.1.0]hexene-type nucleosides structurally similar to D4T and carbovir. A structural analysis and biological activities are discussed.     

Synthesis of 2-Deoxy-β-D-ribose 1-Phosphate,NMR Comparison and Its Enzymatic Activity for Structural Elucidation of Synthetic α-Isomer

Abstract

2-Deoxy-β-D-ribose 1-phosphate (1) was synthesized in a stereoselective manner and isolated with no detectable contamination by its α-isomer (4). Explicit configuration of 4 was first determined by NMR comparison with 1 judging from NOE results and their coupling constants. Natural purine nucleoside phosphorylase (PNPase) did not recognize 1 and gave no products such as α- or β-deoxynucleosides.     

IDENTIFICATION OF CAROTENOIDS PRODUCED FROM CHEESE WHEY BY BLAKESLEA TRISPORA IN SUBMERGED FERMENTATION

The identification of carotenoids in B. trispora during pigment production from deproteinized hydrolyzed whey supplemented with plant oils was studied. The carotenoid content in Blakeslea trispora were β-carotene, γ-carotene, and lycopene. The composition of carotenoids depends of the amount of oils added to the cheese whey. At the maximum concentration of carotenoids, the proportions of β-carotene, γ-carotene, and lycopene (as percent of total carotenoids) was 60.1%, 32.5%, and 7.4%, respectively.     

α-LNA (α-D-Configured Locked Nucleic Acid)

Abstract

Two pyrimidine α-LNA nucleoside monomers have been synthesised and incorporated into α-configured oligonucleotides. A fully modified mixed α-LNA sequence displays unprecedented parallel stranded hybridisation with complementary RNA and a remarkable selectivity for RNA over DNA. Modelling shows α-LNA : RNA to form an extended duplex with a very broad major groove.