Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Inorg Chem ; 63(21): 9931-9940, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38738860

RESUMO

A series of mixed ligand, photoluminescent organometallic Ir(III) complexes have been synthesized to incorporate substituted 2-phenyl-1H-naphtho[2,3-d]imidazole cyclometalating ligands. The structures of three example complexes were categorically confirmed using X-ray crystallography each sharing very similar structural traits including evidence of interligand hydrogen bond contacts that account for the shielding effects observed in the 1H NMR spectra. The structural iterations of the cyclometalated ligand provide tuning of the principal electronic transitions that determine the visible absorption and emission properties of the complexes: emission can be tuned in the visible region between 550 and 610 nm and with triplet lifetimes up to 10 µs. The nature of the emitting state varies across the series of complexes, with different admixtures of ligand-centered and metal-to-ligand charge transfer triplet levels evident. Finally, the use of the complexes as photosensitizers in triplet-triplet annihilation energy upconversion (TTA-UC) was investigated in the solution state. The study showed that the complexes possessing the longest triplet lifetimes showed good viability as photosensitizers in TTA-UC. Therefore, the use of an electron-withdrawing group on the 2-phenyl-1H-naphtho[2,3-d]imidazole ligand framework can be used to rationally promote TTA-UC using this class of complex.

2.
J Lipid Res ; 63(6): 100208, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35436499

RESUMO

The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses.


Assuntos
COVID-19 , Antissépticos Bucais , Antivirais , Cetilpiridínio , Humanos , Lipídeos , Antissépticos Bucais/farmacologia , Povidona-Iodo , RNA Viral , SARS-CoV-2
3.
J Am Chem Soc ; 143(11): 4451-4464, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33719443

RESUMO

The donor-acceptor ability of frustrated Lewis pairs (FLPs) has led to widespread applications in organic synthesis. Single electron transfer from a donor Lewis base to an acceptor Lewis acid can generate a frustrated radical pair (FRP) depending on the substrate and energy required (thermal or photochemical) to promote an FLP into an FRP system. Herein, we report the Csp3-Csp cross-coupling reaction of aryl esters with terminal alkynes using the B(C6F5)3/Mes3P FLP. Significantly, when the 1-ethynyl-4-vinylbenzene substrate was employed, the exclusive formation of Csp3-Csp cross-coupled products was observed. However, when 1-ethynyl-2-vinylbenzene was employed, solvent-dependent site-selective Csp3-Csp or Csp3-Csp2 cross-coupling resulted. The nature of these reaction pathways and their selectivity has been investigated by extensive electron paramagnetic resonance (EPR) studies, kinetic studies, and density functional theory (DFT) calculations both to elucidate the mechanism of these coupling reactions and to explain the solvent-dependent site selectivity.

4.
Chemistry ; 26(17): 3661-3687, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-31709642

RESUMO

The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.


Assuntos
Racemases e Epimerases/química , Albumina Sérica/química , Cinética , Estereoisomerismo
5.
Angew Chem Int Ed Engl ; 57(4): 982-985, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29072355

RESUMO

Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1 H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second-order rate constants for general-base-catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.

6.
Chemistry ; 23(23): 5467-5477, 2017 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-28072487

RESUMO

With the long-term aim of enhancing the binding properties of dinuclear RuII -based DNA light-switch complexes, a series of eight structurally related mono- and dinuclear systems are reported in which the linker of the bridging ligand has been modulated. These tethered systems have been designed to explore issues of steric demand at the binding site and the thermodynamic cost of entropy loss upon binding. Detailed spectroscopic and isothermal titration calorimetry (ITC) studies on the new complexes reveal that one of the linkers produces a dinuclear system that binds to duplex DNA with an affinity (Kb >107 m-1 ) that is higher than its corresponding monometallic complex and is the highest affinity for a non-threading bis-intercalating metal complex. These studies confirm that the tether has a major effect on the binding properties of dinuclear complexes containing intercalating units and establishes key design rules for the construction of dinuclear complexes with enhanced DNA binding characteristics.


Assuntos
Complexos de Coordenação/química , DNA/química , Substâncias Intercalantes/química , Rutênio/química , Sítios de Ligação , Ligantes , Espectroscopia de Ressonância Magnética
7.
Analyst ; 142(6): 987-993, 2017 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-28256648

RESUMO

G-quadruplex sequences exist in eukaryotic organisms and prokaryotes, and the investigation of the interactions between G-quadruplexes and small molecule ligands is important for gene therapy, biosensor fabrication, fluorescence imaging and so on. Here, we investigated the behaviour of methylene blue (MB), an electroactive molecule, in the presence of different intramolecular G-quadruplexes by an electrochemical method using a miniaturized electrochemical device based on its intrinsic electrochemical properties. Although the effects of MB on different intramolecular G-quadruplex structures are not obvious by circular dichroism spectroscopy, distinct differences in the binding affinities of MB with different intramolecular G-quadruplexes were quickly and easily observed by an electrochemical technique. At the same time, for the human telomerase G-rich sequence (HT), the diffusion current of MB changed sensitively under different ionic conditions due to the formation of different conformations of HT, which indicated that our electrochemical method has the potential to study the influence of metal ions on the conformations of the G-quadruplexes with simplicity, rapid response and low cost. From all these, a new stacking mechanism and rule were obtained, which were also validated by docking studies and isothermal titration calorimetry (ITC).


Assuntos
Quadruplex G , Azul de Metileno/química , Técnicas Biossensoriais , Calorimetria , Dicroísmo Circular , Técnicas Eletroquímicas , Humanos , Simulação de Acoplamento Molecular , Telomerase/química
8.
Angew Chem Int Ed Engl ; 56(41): 12628-12633, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28834038

RESUMO

Using a new mononuclear "building block," for the first time, a dinuclear RuII (dppn) complex and a heteroleptic system containing both RuII (dppz) and RuII (dppn) moieties are reported. The complexes, including the mixed dppz/dppn system, are 1 O2 sensitizers. However, unlike the homoleptic dppn systems, the mixed dppz/dppn complex also displays a luminescence "switch on" DNA light-switch effect. In both cisplatin sensitive and resistant human ovarian carcinoma lines the dinuclear complexes show enhanced uptake compared to their mononuclear analogue. Thanks to a favorable combination of singlet oxygen generation and cellular uptake properties all three of the new complexes are phototoxic and display potent activity against chemotherapeutically resistant cells.


Assuntos
Complexos de Coordenação/farmacologia , Substâncias Intercalantes/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Rutênio/farmacologia , Linhagem Celular Tumoral , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , DNA/metabolismo , Feminino , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacocinética , Neoplasias Ovarianas/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Rutênio/química , Rutênio/farmacocinética , Oxigênio Singlete/metabolismo
9.
Chemistry ; 22(18): 6314-22, 2016 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-26997208

RESUMO

The interactions of the water-soluble tetraazaperopyrene dye 1 with ct-DNA, duplex-[(dAdT)12 ⋅(dAdT)12 ], duplex-[(dGdC)12 ⋅(dGdC)12 ] as well as with two G-quadruplex-forming sequences, namely the human telomeric 22AG and the promotor sequence c-myc, were investigated by means of UV/visible and fluorescence spectroscopy, isothermal titration calorimetry (ITC) and molecular docking studies. Dye 1 exhibits a high affinity for G-quadruplex structures over duplex DNA structures. Furthermore, the ligand shows promising G-quadruplex discrimination, with an affinity towards c-myc of 2×10(7) m(-1) (i.e., Kd =50 nm), which is higher than for 22AG (4×10(6) m(-1) ). The ITC data reveal that compound 1 interacts with c-myc in a stoichiometric ratio of 1:1 but also indicate the presence of two identical lower affinity secondary binding sites per quadruplex. In 22AG, there are two high affinity binding sites per quadruplex, that is, one on each side, with a further four weaker binding sites. For both quadruplex structures, the high affinity interactions between compound 1 and the quadruplex-forming nucleic acid structures are weakly endothermic. Molecular docking studies suggest an end-stacking binding mode for compound 1 interacting with quadruplex structures, and a higher affinity for the parallel conformation of c-myc than for the mixed-hybrid conformation of 22AG. In addition, docking studies also suggest that the reduced affinity for duplex DNA structures is due to the non-viability of an intercalative binding mode.


Assuntos
Corantes/química , DNA/química , Sítios de Ligação , Dicroísmo Circular , Quadruplex G , Simulação de Acoplamento Molecular , Solubilidade , Espectrometria de Fluorescência , Água
11.
Chem Sci ; 14(40): 10994-10996, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37860646

RESUMO

Chemists know the value of looking at a reaction for clues about reaction progress and success, but what-it-looks-like has never been quantified. Reid and co-workers (C. Yan, M. Cowie, C. Howcutt, K. M. P. Wheelhouse, N. S. Hodnett, M. Kollie, M. Gildea, M. H. Goodfellow and M. Reid, Chem. Sci., 2023, 14, 5323-5331, https://doi.org/10.1039/d2sc05702f) have developed an approach that uses camera footage of reactions to obtain quantitative descriptors of changes in reaction mixtures to support kinetic analysis.

12.
Biomolecules ; 13(9)2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37759766

RESUMO

Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including Pseudomonas aeruginosa. Previous studies suggested that the disruption of calcium (Ca2+)-DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca2+ binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca2+ binding properties were prepared. Fourier-transform infrared spectroscopy demonstrated prolonged binding of alginate oligosaccharides to the pseudomonal cell membrane even after hydrodynamic shear treatment. Molecular dynamics simulations and isothermal titration calorimetry revealed that OligoG exhibited stronger interactions with bacterial LPS than OligoM, although this difference was not mirrored by differential reductions in bacterial growth. While confocal laser scanning microscopy showed that both agents demonstrated similar dose-dependent reductions in biofilm formation, OligoG exhibited a stronger QS inhibitory effect and increased potentiation of the antibiotic azithromycin in minimum inhibitory concentration and biofilm assays. This study demonstrates that the anti-microbial effects of alginate oligosaccharides are not purely influenced by Ca2+-dependent processes but also by electrostatic interactions that are common to both G-block and M-block structures.


Assuntos
Alginatos , Pseudomonas aeruginosa , Peso Molecular , Relação Estrutura-Atividade , Alginatos/farmacologia , Antibacterianos/farmacologia
13.
Langmuir ; 28(5): 2436-47, 2012 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-22204384

RESUMO

A range of near-monodisperse, multimicrometer-sized polymer particles has been coated with ultrathin overlayers of polypyrrole-palladium (PPy-Pd) nanocomposite by chemical oxidative polymerization of pyrrole using PdCl(2) as an oxidant in aqueous media. Good control over the targeted PPy-Pd nanocomposite loading is achieved for 5.2 µm diameter polystyrene (PS) particles, and PS particles of up to 84 µm diameter can also be efficiently coated with the PPy-Pd nanocomposite. The seed polymer particles and resulting composite particles were extensively characterized with respect to particle size and size distribution, morphology, surface/bulk chemical compositions, and conductivity. Laser diffraction studies of dilute aqueous suspensions indicate that the polymer particles disperse stably before and after nanocoating with the PPy-Pd nanocomposite. The Fourier transform infrared (FT-IR) spectrum of the PS particles coated with the PPy-Pd nanocomposite overlayer is dominated by the underlying particle, since this is the major component (>96% by mass). Thermogravimetric and elemental analysis indicated that PPy-Pd nanocomposite loadings were below 6 wt %. The conductivity of pressed pellets prepared with the nanocomposite-coated particles increased with a decrease of particle diameter because of higher PPy-Pd nanocomposite loading. "Flattened ball" morphologies were observed by scanning/transmission electron microscopy after extraction of the PS component from the composite particles, which confirmed a PS core and a PPy-Pd nanocomposite shell morphology. X-ray diffraction confirmed the production of elemental Pd and X-ray photoelectron spectroscopy studies indicated the existence of elemental Pd on the surface of the composite particles. Transmission electron microscopy confirmed that nanometer-sized Pd particles were distributed in the shell. Near-monodisperse poly(methyl methacrylate) particles with diameters ranging between 10 and 19 µm have been also successfully coated with PPy-Pd nanocomposite, and stable aqueous dispersions were obtained. The nanocomposite particles functioned as an efficient catalyst for the aerobic oxidative homocoupling reaction of 4-carboxyphenylboronic acid in aqueous media for the formation of carbon-carbon bonds. The composite particles sediment in a short time (

Assuntos
Nanocompostos/química , Compostos Organometálicos/química , Paládio/química , Polímeros/química , Pirróis/química , Catálise , Oxirredução , Tamanho da Partícula , Propriedades de Superfície
14.
Chem Sci ; 11(6): 1599-1606, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32206278

RESUMO

A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (λ ex = 550 nm; λ em = 677 nm) cyclometalated organometallic iridium(iii) complex to give the conjugate Ir-CMYC. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18-24 h incubation show that Ir-CMYC concentrations of 80-100 µM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(iii) complex lacking the peptide sequence, Ir-PYR, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 µM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that Ir-PYR and Ir-CMYC display similarly low affinities for DNA (ca. 103 M-1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of Ir-CMYC are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex.

15.
Methods Mol Biol ; 1964: 169-183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30929243

RESUMO

I2CITC allows the analysis of isothermal titration calorimetry (ITC) data for complex coupled equilibria. Here we describe how, using I2CITC, ITC data for systems involving a self-aggregating ligand and a host offering one or two binding sites can be analyzed, how interaction models can be tested, and how confidence intervals for the optimized parameters can be determined.


Assuntos
Calorimetria/métodos , Termodinâmica , Sítios de Ligação , Ligantes , Ligação Proteica
16.
Expert Opin Drug Discov ; 14(6): 527-539, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30882254

RESUMO

INTRODUCTION: Racemization has long been an ignored risk in drug development, probably because of a lack of convenient access to good tools for its detection and an absence of methods to predict racemization risk. As a result, the potential effects of racemization have been systematically underestimated. Areas covered: Herein, the potential effects of racemization are discussed through a review of drugs for which activity and side effects for both enantiomers are known. Subsequently, drugs known to racemize are discussed and the authors review methods to predict racemization risk. Application of a method quantitatively predicting racemization risk to databases of compounds from the medicinal chemistry literature shows that success in clinical trials is negatively correlated with racemization risk. Expert opinion: It is envisioned that a quantitative method of predicting racemization risk will remove a blind spot from the drug development pipeline. Removal of the blind spot will make drug development more efficient and result in less late-stage attrition of the drug pipeline.


Assuntos
Química Farmacêutica/métodos , Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , Desenho de Fármacos , Humanos , Preparações Farmacêuticas/química , Estereoisomerismo
17.
J Inorg Biochem ; 102(4): 673-83, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18055017

RESUMO

The substituted tris(bipyridine)ruthenium(II) complexes {[Ru(bpy)(2)(4,4'-bbob)](2+) and [Ru(bpy)(2)(5,5'-bbob)](2+) [where bpy=2,2'-bipyridine and bbob=bis(benzoxazol-2-yl)-2,2'-bipyridine] have been prepared and compared to the previously studied complex [Ru(bpy)(2)(4,4'-bbtb)](2+) [where bbtb=bis(benzothiazol-2-yl)-2,2'-bipyridine]. From the UV/VIS titration studies, Delta-[Ru(bpy)(2)(4,4'-bbob)](2+) displays a stronger association than the Lambda-isomer with calf-thymus DNA (ct-DNA). For [Ru(bpy)(2)(5,5'-bbob)](2+), there appears to be minimal interaction with ct-DNA. The results of fluorescence titration studies suggest that [Ru(bpy)(2)(4,4'-bbob)](2+) gives an increase in emission intensity with increasing ct-DNA concentrations, with an enantiopreference for the Delta isomer, confirmed by membrane dialysis studies. The fluorescent intercalation displacement studies revealed that [Ru(bpy)(2)(4,4'-bbob)](2+) and [Ru(bpy)(2)(5,5'-bbob)](2+) display a preference for more open DNA structures such as bulge and hairpin sequences. While Lambda-[Ru(bpy)(2)(4,4'-bbtb)](2+) has shown the most significant affinity for all the oligonucleotides sequences screened in previous studies, it is the Delta isomer of the comparable benzoxazole ruthenium(II) complex (Delta-[Ru(bpy)(2)(4,4'-bbob)](2+)) that preferentially binds to DNA.


Assuntos
Benzotiazóis/química , Benzoxazóis/química , DNA/química , Compostos de Rutênio/química , Animais , Bovinos , Análise Espectral
18.
Artigo em Inglês | MEDLINE | ID: mdl-29977590

RESUMO

Acquisition of a mucoid phenotype by Pseudomonas sp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn = 3200 g mol-1) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoid Pseudomonas aeruginosa (NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining. Structural changes in treated biofilms were quantified using COMSTAT image-analysis software of CLSM z-stack images, and nanoparticle diffusion. Interactions between the oligomers, Ca2+ and DNA were studied using molecular dynamics (MD) simulations, Fourier transform infrared spectroscopy (FTIR) and isothermal titration calorimetry (ITC). Imaging demonstrated that OligoG treatment (≥0.5%) inhibited biofilm formation, revealing a significant reduction in both biomass and biofilm height (P < 0.05). TxRd®-labelled oligomers readily diffused into established (24 h) biofilms. OligoG treatment (≥2%) induced alterations in the EPS of established biofilms; significantly reducing the structural quantities of EPS polysaccharides, and extracellular (e)DNA (P < 0.05) with a corresponding increase in nanoparticle diffusion (P < 0.05) and antibiotic efficacy against established biofilms. ITC demonstrated an absence of rapid complex formation between DNA and OligoG and confirmed the interactions of OligoG with Ca2+ evident in FTIR and MD modelling. The ability of OligoG to diffuse into biofilms, potentiate antibiotic activity, disrupt DNA-Ca2+-DNA bridges and biofilm EPS matrix highlights its potential for the treatment of biofilm-related infections.

19.
Sci Rep ; 7: 44731, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28361894

RESUMO

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.


Assuntos
Alginatos/farmacologia , Anti-Infecciosos/farmacologia , Membrana Celular/metabolismo , Pseudomonas aeruginosa/citologia , Streptococcus mutans/citologia , Alginatos/química , Cátions Bivalentes/farmacologia , Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Ácido Glucurônico/química , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Lipopolissacarídeos/química , Lipopolissacarídeos/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos
20.
Chem Commun (Camb) ; (33): 3516-8, 2006 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-16921430

RESUMO

Incorporation of a bicyclic cytosine analogue, 3-beta-D-(2'-deoxyribofuranosyl)-7,8-dihydropyrido[2,3-d]pyrimidine, into synthetic DNA duplexes results in a greatly enhanced thermal stability (3-4 degrees C per modification) compared to the corresponding unmodified duplex.


Assuntos
Compostos Bicíclicos com Pontes/química , Citosina/análogos & derivados , Quebras de DNA de Cadeia Dupla , DNA/química , Sequência de Bases , Citosina/síntese química , Citosina/química , Modelos Químicos , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Termodinâmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA