Heteroassociation of antibiotic norfloxacin with aromatic vitamins in aqueous solution

Heteroassociation of antibacterial antibiotic norfloxacin with aromatic vitamins nicotinamide and flavin mononucleotide in aqueous solution was studied by ¹H NMR spectroscopy (500 MHz). Equilibrium constants, induced proton chemical shifts, and thermodynamic parameters (ΔH, ΔS) for the reactions of heteroassociation of the molecules were determined on the basis of the concentration and temperature dependences of proton chemical shifts for interacting aromatic molecules. The analysis of the results obtained indicates the formation of heterocomplexes between vitamin molecules and norfloxacin owing to stacking interactions between aromatic chromophores and additional intermolecular hydrogen bonding in norfloxacin-nicotinamide. The most probable spatial structures of 1:1 norfloxacin-flavin mononucleotide and norfloxacin-nicotinamide heterocomplexes were determined by molecular modeling methods using X-PLOR software on the basis of analysis of induced proton chemical shifts.     

Heteroassociation of antibiotic norfloxacin with aromatic vitamins in aqueous solution

The heteroassociation of the antibacterial antibiotic norfloxacin with aromatic vitamins nicotineamide and flavin mononucleotide in aqueous solution has been studied by 1H NMR spectroscopy (503 MHz). Equilibrium constants, induced proton chemical shifts, and the thermodynamic parameters (deltaH, deltaS) of the heteroassociation of molecules were determined from the concentration and temperature dependences of chemical shifts of protons of interacting aromatic molecules. An analysis of the results indicates the formation of heterocomplexes between the molecules of the vitamins and norfloxacin, which is caused by stacking interactions between aromatic chromophores and an additional intermolecular hydrogen bond in the norfloxacin-nicotinamide system. Based on the analysis of induced chemical shifts of protons of molecules, the most probable spatial structures 1:1 of norfloxacin-flavin mononucleitide and norfloxacin-nicotinamide heterocomolexes were determined by the methods of molecular modeling using the X-PLOR program.     

Interaction between aromatic antibiotics and vitamins: 1H NMR analysis of the heteroassociation of nicotinamide and anthracycline antitumor antibiotics

The interaction between anthracycline antitumor antibiotics daunomycin and novatrone and the vitamin nicotinamide has been investigated by one- and two-dimensional 1H NMR spectroscopy (500 MHz). Due to significant differences in structures of the chromophores of interacting molecules, a two-site heteroassociation model has been developed, allowing the arrangement of one and two nicotinamide molecules on the chromophore of the antibiotic. The equilibrium association constant, thermodynamical parameters (deltaH, deltaS) of the heteroassociation of nicotinamide with daunomycin and novatrone and the induced proton chemical shifts in the heterocomplexes have been determined from the concentration and temperature dependences of proton chemical shifts of interacting molecules. The most favorable structures of 1:1 nicotinamide--daunomycin and nicotinamide-novatrone heteroassociation complexes have been determined using both the molecular mechanics methods (X-PLOR software) and the calculated values of induced proton chemical shifts. Analysis of the results obtained allows one to conclude that two nicotinamide molecules cannot simultaneously bind on one side of the chromophore of antibiotic. Heterocomplexes of the vitamin with the antibiotics with a stoichiometry 1:1 are mainly stabilized by the stacking of aromatic chromophores.     

Studies by means of 1H NMR spectroscopy of complex formation of aromatic biologically active compounds with antibiotic topotecan

The analysis of heteroassociation of antibiotic topotecan (TPT) with aromatic biologically active compounds (BAC): caffeine, mutagens ethidium bromide and proflavine, antibiotic daunomycin, vitamins flavin-mononucleotide and nicotinamide, has been carried out in the work using 1H NMR spectroscopy data. The equilibrium constants of heteroassociation and induced chemical shifts of the protons have been obtained in the complexes with BAC. It is found that the complex formation TPT-BAC has the nature of stacking of the chromophores, additionally stabilized in the case of proflavine by intermolecular hydrogen bond. Calculation of the basic components of the Gibbs free energy of the complexation reactions is carried out, and the factors which stabilize and destabilize the heterocomplexes of molecules are revealed.     

Muscle transcriptomic analyses in Angus cattle with divergent tenderness

Beef tenderness contributes significantly to variation of beef palatability, and is largely influenced by various genetic and environmental factors. To identify candidate genes and pathways related to beef tenderness, we analyzed the longissimus dorsi (LD) muscle of Angus cattle that had different degrees of tenderness, measured by Warner-Bratzler shear force (WBSF). Microarray and RT-PCR analyses identified 53 genes that were differentially expressed in LD samples categorized as either tough or tender, including myosin, heavy chain 3 skeletal muscle embryonic (MYH3), myosin heavy chain 8 skeletal muscle perinatal (MYH8), guanylate binding protein 5 (GBP5), fatty acid binding protein 4 (FABP4), Stearoyl-coenzyme A desaturase (SCD), Fatty acid synthase (FASN), ubiquitin-like with PHD and ring finger domains 1 (UHRF1). Most of these genes are involved in lipid metabolism and skeletal muscle contraction. Employing Gene ontology (GO) and Ingenuity Pathway Analysis (IPA), several GO terms and pathways were found to be related to hydrolase, peptidase and GTPase activity, lipid metabolism, small molecule biochemistry, molecular transport, and tissue development. Overall, this analysis provides insight into the metabolic relationships between muscle biology and beef quality.     

The role of slow potassium current in phenomena of voltage-dependent action of 4-aminopyridine in amphibian myelinated nerve fibres

The mechanism underlying the voltage-dependent action of 4-aminopyridine (4-AP) is investigated in experiments on amphibian myelinated nerve fibres (Rana ridibunda Pallas) by way of extracellular recording of electrical activity and using activators of potassium current (potassium-free solution and nitric oxide NO) and inhibitors of sodium current (tetrodotoxin). Measurement of action potential (AP) areas was used to evaluate the extent of general membrane depolarization during the activity of nerve fibres. Tetrodotoxin-induced decrease in general membrane depolarization (when the action potential amplitude was reduced by less than 20%) leads to an increase in the duration of depolarizing after-potential (DAP). This supports the dependence of time course of DAP in the presence of 4-AP on ratio of fast and slow potassium channels. In the absence of 4-AP, potassium-free solution and NO increase the potassium current through fast potassium channels (decreasing AP duration, reducing DAP and sometimes producing fast hyperpolarizing after-potential (HAP) after shortened AP), and in the presence of 4-AP these activators increase potassium current through unblocked slow potassium channels (making the development of slow HAP induced by 4-AP more rapid). The increase of slow HAP induced by 4-AP under the influence of potassium-free solution with NO supports the idea that slow HAP is due to activation of slow potassium channels and argues against the notion of removal of block of fast potassium channels. All analyzed phenomena of voltage-dependent action of 4-AP in amphibian myelinated nerve fibers can be accounted for by the activation of slow potassium current produced by membrane depolarization and a decrease of the amount of fast potassium channels involved in the membrane repolarization.     

1H NMR study of the complexation of the quinolone antibiotic norfloxacin with DNA

Complexation of antibiotic norfloxacin (NOR) with DNA fragments 5'-d(TpGpCpA) and 5'-d(CpGpCpG) has been studied in aqueous solution by 1H NMR spectroscopy (500 MHz). Equilibrium parameters of the complexation with single-stranded and duplex forms of DNA oligomer--equilibrium constants, enthalpy and entropy--have been obtained for the first time. Based on the analysis of the complexation parameters as well as induced chemical shifts of the antibiotic protons within different complexes, it was found that NOR binds with the tetramer duplexes mainly by intercalation. The complexation with the single-stranded form may occur either by intercalation and external binding. The site of preferential binding of the antibiotic with DNA duplex is GC site.     

重庆市蕨类植物区系调查和分析

重庆市有野生蕨类植物47科120属604种(含变种及以下分类单位)。其科属优势明显,其中蹄盖蕨科、金星蕨科、鳞毛蕨科和水龙骨科4个科包含了49属337种,占重庆市蕨类植物属、种总数的40.83%和55.79%;特有现象明显,地方特有种十分丰富,中国特有种和地方特有种类分别达到164种和33种;蕨类植物区系具有古老、孑遗和原始性等特点,表现出一定的热带性质或热带亲缘。     

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

The entire family of noncomplementary hexamer oligodeoxyribonucleotides d(GCXYGC) (X and Y = A, G, C, or T) were assessed for topological indicators and equilibrium thermodynamics using a priori molecular modeling and solution phase NMR spectroscopy. Feasible modeled hairpin structures formed a basis from which solution structure and equilibria for each oligonucleotide were considered. ¹H and ³¹P variable temperature‐dependent (VT) and concentration‐dependent NMR data, NMR signal assignments, and diffusion parameters led to d(GCGAGC) and d(GCGGGC) being understood as exceptions within the family in terms of self‐association and topological character. A mean diffusion coefficient D_{298 K} = (2.0 ± 0.07) × 10^?10 m² s^?1 was evaluated across all hexamers except for d(GCGAGC) (D_{298 K} = 1.7 × 10^?10 m² s^?1) and d(GCGGGC) (D_{298 K} = 1.2 × 10^?10 m² s^?1). Melting under VT analysis (T_m = 323 K) combined with supporting NMR evidence confirmed d(GCGAGC) as the shortest tandem sheared GA mismatched duplex. Diffusion measurements were used to conclude that d(GCGGGC) preferentially exists as the shortest stable quadruplex structure. Thermodynamic analysis of all data led to the assertion that, with the exception of XY = GA and GG, the remaining noncomplementary oligonucleotides adopt equilibria between monomer and duplex, contributed largely by monomer random‐coil forms. Contrastingly, d(GCGAGC) showed preference for tandem sheared GA mismatch duplex formation with an association constant K = 3.9 × 10⁵M^?1. No direct evidence was acquired for hairpin formation in any instance although its potential existence is considered possible for d(GCGAGC) on the basis of molecular modeling studies. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 1023–1038, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

1H NMR analysis of the complex formation of aromatic molecules of antibiotic and vitamin in aqueous solution: heteroassociation of actinomycin D and flavin mononucleotide

The molecular mechanism of the combined action of antibiotic and vitamin was studied by NMR spectroscopy. The heteroassociation of the antitumor antibiotic actinomycin D and flavin mononucleotide was investigated as a function of concentration and temperature by 500 MHz 1H NMR spectroscopy. The equilibrium association constant, the thermodynamic parameters (deltaH, deltaS) of heteroassociation of actinomycin D with flavin mononucleotide, and the limiting values of proton chemical shifts in the heterocomplex were determined from the concentration and temperature dependences of proton chemical shifts of molecules. The most favorable structure of the 1:1 actinomycin D-flavin mononucleotide heteroassociation complex was determined using both the molecular mechanics methods (X-PLOR software) and the limiting values of proton chemical shifts of the molecules. In the calculated structure, the planes of the chromophores of actinomycin D and flavin mononucleotide molecules in the 1:1 heterocomplex are parallel and separated from each other by a distance of about 0.34 nm. At the same time, there is a probability of formation of intermolecular hydrogen bonds in the calculated structure of 1:1 actinomycin D-flavin mononucleotide complex. The analysis of the results obtained suggests that aromatic molecules of vitamins, e.g., flavin mononucleotide, can form energetically favorable heterocomplexes with aromatic antitumor antibiotics in aqueous solution, modulating thereby the efficacy of their medical and biological action.