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1.
Medicine (Baltimore) ; 99(5): e18898, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000393

RESUMO

BACKGROUND: A recent study has reported that there are >240 million patients infected with chronic hepatitis B (CHB) worldwide. Once patients with CHB start antiviral treatment, they need to take antiviral drugs for a long period, which may lead to a series of side effects, and the resistance to the antiviral drugs may also emerge. We aim to evaluate the efficacy and safety of kushenin (KS) combined with entecavir (ETV) for chronic hepatitis B. METHODS: Randomized controlled trials (RCTs) of KS combined with ETV for CHB will be identified from PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Chongqing VIP, Wangfang Data. Literature screening and data extraction will be independently performed by 2 researchers. The cochrane collaboration tool for assessing risk of bias will be applied to evaluate the risk of bias of the RCTs included. The extracted data will be analyzed by Rev-man 5.3.0 software. RESULTS: A high-quality synthesis of current evidence on the efficacy and safety of KS combined with ETV for CHB will be provided in this study. CONCLUSION: This systematic review will aim to evaluate the efficacy and safety of KS combined with ETV for CHB. PROSPERO REGISTRATION NUMBER: CRD42019124790.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Pterocarpanos/uso terapêutico , Quimioterapia Combinada , Guanina/uso terapêutico , Humanos , Metanálise como Assunto , Fitoterapia , Sophora , Revisão Sistemática como Assunto
2.
Phys Chem Chem Phys ; 22(2): 838-853, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31840715

RESUMO

The five fundamental units of the genetic code: uracil (U), thymine (T), cytosine (C), adenine (A) and guanine (G) are known for extremely low vapor pressure and low thermal stability at elevated temperatures. Therefore, application of conventional techniques for the determination of sublimation enthalpies and vapor pressures fails to provide accurate results. Recently, a Fast Scanning Calorimetry method (FSC) for vapor pressure determination was developed for investigation of extremely low volatile, as well as for thermally unstable molecular and ionic molecules. This success has encouraged application of the FSC method for determination of vapor pressures and sublimation enthalpies of the five nucleobases, where available literature data are in disarray. The thermodynamic data of the nucleobases available in the literature were collected, evaluated, and combined with our experimental results to reconcile available experimental data. The set of evaluated thermochemical data on the five nucleobases was recommended as the benchmark properties for these thermally labile compounds.


Assuntos
Adenina/química , Calorimetria , Citosina/química , Guanina/química , Termodinâmica , Timina/química , Uracila/química , Pressão , Volatilização
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117380, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31344581

RESUMO

In this work, we report the sensitive and selective sensing of the purine bases adenine and guanine in urine matrix by using surface-enhanced Raman spectroscopy (SERS) and a colloidal SERS substrate. To identify suitable conditions for quantitative analysis, the pH dependence of spectra of adenine, guanine, urine simulant and their mixtures was studied on gold nanoparticles suspension. Interestingly, although the urine matrix promotes the analytes signal suppression and overlapping bands, it can also cause an improvement in repeatability of the SERS measurements. This effect was associated to the relatively controlled formation of small-sized gold clusters and it was investigated both experimentally and theoretically. Furthermore, a correlation constrained multivariate curve resolution-alternating least squares (MCR-ALS) method was developed to resolve overlapping SERS bands and to quantify physiologically relevant (micromolar) concentrations of the bioanalytes. The performance of the proposed MCR-ALS approach (assessed in terms of figures of merit) was similar to that obtained by using partial least squares regression, but with the additional advantage of retrieving valuable spectral information. Therefore, this method can be used for improving selectivity of colloidal clusters in qualitative and quantitative SERS analysis of complex media, avoiding the need for tedious nanoparticle-surface modification or preliminary chromatographic separation.


Assuntos
Coloide de Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Adenina/urina , Guanina/urina , Humanos , Análise dos Mínimos Quadrados , Modelos Químicos , Análise Multivariada
5.
Medicine (Baltimore) ; 98(51): e18458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861022

RESUMO

BACKGROUND: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis. METHOD: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination.PROSPERO registration number: CRD42019135402.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/análogos & derivados , Hepatite B/complicações , Cirrose Hepática/tratamento farmacológico , Biomarcadores/sangue , Quimioterapia Combinada , Guanina/uso terapêutico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Revisão Sistemática como Assunto
7.
J Chem Theory Comput ; 15(12): 6984-6991, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31665604

RESUMO

A double proton transfer reaction in a guanine-cytosine (GC) base pair has been proposed as a possible mechanism for rare tautomer (G*C*) formation and thus a source of spontaneous mutations. We analyze this system with free energy calculations based on extensive Quantum Mechanics/Molecular Mechanics simulations to properly consider the influence of the DNA biomolecular environment. We find that, although the G*C* rare tautomer is metastable in the gas phase, it is completely unstable in the conditions found in cells. Thus, our calculations show that a double proton reaction cannot be the source of spontaneous point mutations. We have also analyzed the intrabase H transfer reactions in guanine. Our results show that the DNA environment gives rise to a large free energy difference between the rare and canonical tautomers. These results show the key role of the DNA biological environment for the stability of the genetic code.


Assuntos
Pareamento de Bases , Citosina/química , DNA de Forma B/química , Guanina/química , Prótons , Teoria Quântica
8.
Phys Chem Chem Phys ; 21(41): 22857-22868, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31599896

RESUMO

Three low-energy isomers of 9-methylguanine, the amino-oxo (AO) form and two amino-hydroxy (AH1 and AH2) conformers, were trapped from the gas phase into low-temperature argon matrices. The AH1 and AH2 isomers, differing in the orientation of the OH group, were found to transform into each other upon excitation with near-IR light. The population of the AO form of the compound was not changed upon any near-IR irradiation of the matrix samples. Using monochromatic near-IR light, generated by a frequency-tunable laser source, it was possible to selectively induce the AH1 → AH2 or AH2 → AH1 conversion. Photoreversibility of this conformational transformation was then demonstrated. Exposure of matrix-isolated monomers of 9-methylguanine to broadband near-IR light also led to conformational conversions within the amino-hydroxy tautomeric form; the final stage of this process was always the same photostationary state independent of the initial ratio of AH1 and AH2 populations. Spontaneous conformational conversion, transforming the higher-energy AH2 form into the lower-energy AH1 isomer, was observed for matrix-isolated monomers of 9-methylguanine kept in the dark. The mechanism of this process must rely on quantum tunneling of the light hydrogen atom. Irradiation of matrix-isolated 9-methylguanine with UV laser light at λ = 288 or 285 nm led to a substantial consumption of the two AH forms, while the amount of AO isomer remained unchanged. On the other hand, a decrease in the population of the AO isomer occurred upon excitations at shorter wavelengths, λ = 280 or 275 nm. The spectral changes observed after UV-irradiation suggest the generation (and stabilization in the matrix) of a radical species, resulting from the photocleavage of the O-H or N1-H bonds, in the AH or AO isomer, respectively.


Assuntos
Argônio/química , Temperatura Baixa , Guanina/análogos & derivados , Raios Infravermelhos , Raios Ultravioleta , Guanina/química , Isomerismo , Conformação Molecular/efeitos da radiação
9.
J Phys Chem Lett ; 10(21): 6771-6779, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31609632

RESUMO

Strand hybridization is not only a fundamental molecular mechanism underlying the biological functions of nucleic acids but is also a key step in the design of efficient nanodevices. Despite recent efforts, the microscopic rules governing the hybridization mechanisms remain largely unknown. In this study, we exploit the energy landscape framework to assess how sequence-specificity modulates the hybridization mechanisms in DNA. We find that GG-tracts hybridize much more rapidly compared to GC-tracts, via either zippering or slithering pathways. For the hybridization of GG-tracts, both zippering and slithering mechanisms appear to be kinetically relevant. In contrast, for the GC-tracts, the zippering mechanism is dominant. Our work reveals that even for the relatively small systems considered, the energy landscapes feature multiple metastable states and kinetic traps, which is at odds with the conventional "all-or-nothing" model of DNA hybridization formulated on the basis of thermodynamic arguments alone. Interestingly, entropic effects are found to play an important role in determining the thermal stability of competing conformational ensembles and in determining the preferred hybridization pathways.


Assuntos
Oligonucleotídeos/química , Guanina/química , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Oligonucleotídeos/metabolismo , Termodinâmica
10.
Phys Chem Chem Phys ; 21(42): 23418-23424, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31624816

RESUMO

DNA-protein cross-links constitute bulky DNA lesions that interfere with the cellular machinery. Amongst these stable covalently tethered adducts, the efficient nucleophilic addition of the free amino group of lysines onto the guanine radical cation has been evidenced. In vitro addition of a trilysine peptide onto a guanine radical cation generated in a TGT oligonucleotide is so efficient that competitive addition of a water molecule, giving rise to 8-oxo-7,8-dihydroguanine, is not observed. This suggests a spatial proximity between guanine and lysine for the stabilization of the prereactive complex. We report all-atom microsecond scale molecular dynamics simulations that probe the structure and interactions of the trilysine peptide (KKK) with two oligonucleotides. Our simulations reveal a strong, electrostatically driven yet dynamic interaction, spanning several association modes. Furthermore, the presence of neighbouring cytosines has been identified as a factor favoring KKK binding. Relying on ab initio molecular dynamics on a model system constituted of guanine and methylammonium, we also corroborate a mechanistic pathway involving fast deprotonation of the guanine radical cation followed by hydrogen transfer from ammonium leaving as a result a nitrogen reactive species that can subsequently cross-link with guanine. Our study sheds new light on a ubiquitous mechanism for DNA-protein cross-links also stressing out possible sequence dependences.


Assuntos
Simulação de Dinâmica Molecular , Oligonucleotídeos/química , Oligopeptídeos/química , Sítios de Ligação , Guanina/química , Lisina/química , Teoria Quântica , Termodinâmica
11.
J Biochem Mol Toxicol ; 33(11): e22396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31557364

RESUMO

The furocoumarin backbone is a promising platform for chemical modifications aimed at creating new pharmaceutical agents. However, the high level of biological activity of furocoumarins is associated with a number of negative effects. For example, some of the naturally occurring ones and their derivatives can show genotoxic and mutagenic properties as a result of their forming crosslinks with DNA molecules. Therefore, a particularly important area for the chemical modification of natural furocoumarins is to reduce the negative aspects of their bioactivity. By studying a group of 21 compounds-1,2,3-triazolyl modified derivatives of furocoumarin and peucedanin-using the SOS chromotest, the Ames test, and DNA-comet assays, we revealed modifications that can neutralize the structure's genotoxic properties. Theoretical aspects of the interaction of the compound library were studied using molecular modeling and this identified the leading role of the polyaromatic molecular core that takes part in stacking-interactions with the pi-systems of the nitrogenous bases of DNA.


Assuntos
Cumarínicos/química , Furocumarinas/química , Substâncias Intercalantes/química , Mutagênicos/química , Extratos Vegetais/química , Allium/citologia , Apiaceae/química , Ensaio Cometa , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Simples/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Guanina/química , Ligações de Hidrogênio , Meristema/efeitos dos fármacos , Simulação de Acoplamento Molecular , Salmonella typhimurium/efeitos dos fármacos
12.
PLoS Comput Biol ; 15(9): e1007383, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31539370

RESUMO

G-quadruplexes (G4) are secondary structures formed by guanine-rich nucleic acid sequences and shown to exist in living cells where they participate in regulation of gene expression and chromosome maintenance. G-quadruplexes with solvent-exposed guanine tetrads show the tendency to associate together through cofacial stacking, which may be important for packaging of G4-forming sequences and allows for the design of higher-order G4 DNA structures. To understand the molecular driving forces for G4 association, here, we study the binding interaction between two parallel-stranded G-quadruplexes using all-atom molecular dynamics simulations. The predicted dimerization free energies show that direct binding through the 5'-G-tetrads is the most preferred of all possible end-to-end stacking orientations, consistently with all available experimental data. Decomposition of dimerization enthalpies in combination with simulations at varying ionic strength further indicate that the observed orientational preferences arise from a fine balance between the electrostatic repulsion of the sugar-phosphate backbones and favorable counterion binding at the dimeric interface. We also demonstrate how these molecular-scale findings can be used to devise means of controlling G4 dimerization equilibrium, e.g., by altering salt concentration and using G4-targeted ligands.


Assuntos
DNA , Quadruplex G , Guanina , Sequência de Bases , Biologia Computacional , Simulação por Computador , DNA/química , DNA/metabolismo , DNA/ultraestrutura , Dimerização , Guanina/química , Guanina/metabolismo , Simulação de Dinâmica Molecular , Termodinâmica
13.
Nucleic Acids Res ; 47(18): 9502-9510, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31504779

RESUMO

Distinct from intermolecular split G-quadruplex (Inter-SG), intramolecular split G-quadruplex (Intra-SG) which could be generated in a DNA spacer-inserted G-quadruplex strand has not been systematically explored. Not only is it essential for the purpose of simplicity of DNA-based bioanalytical applications, but also it will give us hints how to design split G-quadruplex-based system. Herein, comprehensive information is provided about influences of spacer length and split mode on the formation of Intra-SG, how to adjust its thermodynamic stability, and selection of optimal Intra-SG for bioanalysis. For instances, non-classical Intra-SG (e.g. 2:10, 4:8 and 5:7) displays lower stability than classical split strands (3:9, 6:6 and 9:3), which is closely related to integrity of consecutive guanine tract; as compared to regular Intra-SG structures, single-thymine capped ones have reduced melting temperature, providing an effective approach to adjustment of stability. It is believed that the disclosed rules in this study will contribute to the effective application of split G-quadruplex in the field of DNA technology in the future.


Assuntos
DNA Intergênico/genética , DNA/genética , Quadruplex G , Conformação de Ácido Nucleico , Dicroísmo Circular/métodos , DNA/química , DNA Intergênico/química , DNA Intergênico/ultraestrutura , Guanina/química , Termodinâmica , Timina/química
14.
BMJ Case Rep ; 12(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371277

RESUMO

A 70-year-old man presented with 1 month of haematuria and mild right-sided flank pain with no other symptoms. Diagnostic workup included serum studies which showed the presence of antimyeloperoxidase antibodies, a kidney biopsy which demonstrated necrotising crescentic glomerulonephritis with linear immunofluorescence of the basement membrane, and electron microscopy which exhibited thickening of the glomerular basement membrane. Incidentally, the patient was discovered to have a latent hepatitis B infection, which complicated immunosuppressive therapy. He was treated with a course of plasmapheresis and methylprednisolone, followed by entecavir for hepatitis B prophylaxis, and finally by rituximab. This case of glomerulonephritis was notable for its resemblance to the better known Goodpasture's disease. Typically, Goodpasture's syndrome exists on a spectrum from seronegative disease to double-positive disease that presents with both anti-glomerular basement membrane (anti-GBM) and cytoplasmic-antineutrophil cytoplasmic antibodies/antiproteinase 3 antibodies (c-ANCA/anti-PR3). However, this patient's glomerulonephritis was unique because he presented negative for anti-GBM antibodies and positive for perinuclear-antineutrophil cytoplasmic antibodies/antimyeloperoxidase antibodies (p-ANCA/anti-MPO).


Assuntos
Glomerulonefrite/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Peroxidase/imunologia , Idoso , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Autoanticorpos/metabolismo , Diagnóstico Diferencial , Glomerulonefrite/imunologia , Glomerulonefrite/terapia , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Metilprednisolona/uso terapêutico , Microscopia Eletrônica , Plasmaferese , Rituximab/uso terapêutico , Resultado do Tratamento
15.
Appl Microbiol Biotechnol ; 103(19): 8021-8033, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372707

RESUMO

8-oxoguanine (GO) is a major lesion found in DNA that arises from guanine oxidation. The hyperthermophilic and radioresistant euryarchaeon Thermococcus gammatolerans encodes an archaeal GO DNA glycosylase (Tg-AGOG). Here, we characterized biochemically Tg-AGOG and probed its GO removal mechanism by mutational studies. Tg-AGOG can remove GO from DNA at high temperature through a ß-elimination reaction. The enzyme displays an optimal temperature, ca.85-95 °C, and an optimal pH, ca.7.0-8.5. In addition, Tg-AGOG activity is independent on a divalent metal ion. However, both Co2+ and Cu2+ inhibit its activity. The enzyme activity is also inhibited by NaCl. Furthermore, Tg-AGOG specifically cleaves GO-containing dsDNA in the order: GO:C, GO:T, GO:A, and GO:G. Moreover, the temperature dependence of cleavage rates of the enzyme was determined, and from this, the activation energy for GO removal from DNA was first estimated to be 16.9 ± 0.9 kcal/mol. In comparison with the wild-type Tg-AGOG, the R197A mutant has a reduced cleavage activity for GO-containing DNA, whereas both the P193A and F167A mutants exhibit similar cleavage activities for GO-containing DNA. While the mutations of P193 and F167 to Ala lead to increased binding, the mutation of R197 to Ala had no significant effect on binding. These observations suggest that residue R197 is involved in catalysis, and residues P193 and F167 are flexible for conformational change.


Assuntos
DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Análise Mutacional de DNA , Guanina/análogos & derivados , Thermococcus/enzimologia , Ativadores de Enzimas/análise , Inibidores Enzimáticos/análise , Estabilidade Enzimática , Guanina/metabolismo , Concentração de Íons de Hidrogênio , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Temperatura Ambiente
16.
Medicine (Baltimore) ; 98(34): e16943, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441888

RESUMO

BACKGROUND: Chronic hepatitis b (CHB) is a serious problem worldwide. Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) both are first-line drugs for CHB, but there is debate about which is more appropriate in nucleos(t)ide analogue-naive CHB. OBJECTIVE: To systematically evaluate the effectiveness and safety of tenofovir and ETV in nucleos(t)ide analogue-naive CHB. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE, Clinical Trials, and China National Knowledge Infrastructure databases will be electronically searched to collect randomized controlled trials regarding the comparison between tenofovir and ETV in nucleos(t)ide analogue-naive CHB since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software will be used for the meta-analysis. RESULT: We will provide practical and targeted results assessing the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients, try to compare the advantages of TDF and ETV. CONCLUSION: The stronger evidence about the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients will be provided for clinicians. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42019134194.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Guanina/uso terapêutico , Humanos , Metanálise como Assunto , Revisão Sistemática como Assunto
17.
Nucleic Acids Res ; 47(18): 9857-9870, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400119

RESUMO

Of the four bases, guanine is the most susceptible to oxidation, which results in the formation of 8-oxoguanine (8-oxoG). In protein-free DNA, 8-oxodG adopts the syn conformation more frequently than the anti one. In the syn conformation, 8-oxodG base pairs with dA. The equilibrium between the anti and syn conformations of the adduct are known to be altered by the enzyme recognizing 8-oxodG. We previously showed that 8-oxoG in mRNA severely disrupts tRNA selection, but the underlying mechanism for these effects was not addressed. Here, we use miscoding antibiotics and ribosome mutants to probe how 8-oxoG interacts with the tRNA anticodon in the decoding center. Addition of antibiotics and introduction of error-inducing mutations partially suppressed the effects of 8-oxoG. Under these conditions, rates and/or endpoints of peptide-bond formation for the cognate (8-oxoG•C) and near-cognate (8-oxoG•A) aminoacyl-tRNAs increased. In contrast, the antibiotics had little effect on other mismatches, suggesting that the lesion restricts the nucleotide from forming other interactions. Our findings suggest that 8-oxoG predominantly adopts the syn conformation in the A site. However, its ability to base pair with adenosine in this conformation is not sufficient to promote the necessary structural changes for tRNA selection to proceed.


Assuntos
Pareamento de Bases/genética , Guanosina/análogos & derivados , Conformação de Ácido Nucleico , Ribossomos/genética , Antibacterianos/farmacologia , Anticódon/química , Anticódon/genética , Dano ao DNA/genética , Escherichia coli/genética , Guanina/química , Guanosina/química , Guanosina/genética , Mutação/efeitos dos fármacos , Oxirredução , RNA Mensageiro/genética , RNA de Transferência , Aminoacil-RNA de Transferência/efeitos dos fármacos , Ribossomos/química
18.
Anal Chim Acta ; 1079: 86-93, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31387723

RESUMO

The as-prepared SWNTs are always a mixture of metallic (m-) and semiconducting (s-) tubes with quite different electrochemical properties which is a major barrier for their application in many fields. Based on the noncovalent interactions between planar aromatic molecules and SWNTs, the pyrene derivatives 1-docosyloxylmethylpyrene (DomP) was synthesized to separate the m-SWNTs and s-SWNTs via its significant selectivity toward s-SWNTs, i.e. electronic modulation. Before and after doping with electron, the electrochemical properties of s-SWNTs were studied and compared with that of m-SWNTs by electronic absorption spectroscopy, electrochemical impedance spectroscopy and cyclic voltammogram. As demonstrated, the electrocatalytic activity of electron modulated s-SWNTs was significantly improved and even better than m-SWNTs. Thus a novel sensor was constructed with the electron modulated s-SWNTs modified electrode and successfully applied for simultaneous determination of guanine and adenine.


Assuntos
Adenina/análise , Guanina/análise , Nanotubos de Carbono/química , Espectroscopia Dielétrica , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Concentração de Íons de Hidrogênio , Limite de Detecção , Pirenos/síntese química , Pirenos/química
19.
Chem Asian J ; 14(22): 3962-3968, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31389664

RESUMO

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3-deazaneplanocin A, galidesivir, GS-6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS-6620, remdesivir and pyrazofurin) are C-nucleosides, and two of them (GS-6620, remdesivir) also contain a phosphoramidate part. The C-nucleoside and phosphoramidate (and for the adenine analogues the 1'-cyano group as well) may be considered as essential attributes for their antiviral activity.


Assuntos
Adenina/análogos & derivados , Antivirais/química , Guanina/análogos & derivados , Febres Hemorrágicas Virais/tratamento farmacológico , Adenina/farmacologia , Adenina/uso terapêutico , Amidas/química , Amidas/metabolismo , Amidas/farmacologia , Amidas/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Pareamento de Bases , Ebolavirus/efeitos dos fármacos , Guanina/farmacologia , Guanina/uso terapêutico , Humanos , Nucleotídeos/química , Nucleotídeos/uso terapêutico , Ácidos Fosfóricos/química , Ácidos Fosfóricos/uso terapêutico , Pirazinas/química , Pirazinas/metabolismo , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Triazinas/química , Triazinas/uso terapêutico
20.
Phys Chem Chem Phys ; 21(29): 16190-16197, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31298243

RESUMO

Over the past few years, the interest in Resveratrol (3,4',5,-trihydroxystilbene, RSV) has increased due to the evidence found of its antioxidant action that protects biomolecules and cells from oxidative damage. The interest has been further exacerbated by the natural presence of RSV in some fruits and derivatives, especially in red wine. In this paper we present evidence of RSV capacity in protecting a deoxynucleotide, an essential constituent of DNA, from one-electron oxidation. This article evaluates the mechanism responsible for the antioxidant action of RSV, after one-electron oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP), by kinetic analysis during steady-state irradiation and laser flash photolysis experiments. Results showed that RSV protects dGMP by recovering the nucleotide from its radical, which is formed after the reaction of dGMP with the triplet excited state of the photosensitizer. In the absence of RSV, dGMP is irremediably oxidized, and if the damage occurs in dGMP located in DNA molecules, the consequences can be as serious as mutations and subsequent carcinogenic lesions.


Assuntos
Guanina/química , Resveratrol/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Elétrons , Neoplasias/prevenção & controle , Oxirredução/efeitos dos fármacos , Resveratrol/química
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