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1.
J Chromatogr A ; 1621: 461066, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32299623

RESUMO

The ion-exchange and complex forming equilibria were quantitatively described and demonstrated in order to understand major factors in the control of selectivity in the analytical separation of carboxylic acids and inorganic anions in cryptand based ion chromatography. A complex retention model has been developed for the separation on a non-conventional IC column. Changes in retention are treated both theoretically and experimentally. Retention mechanism is employed on a macrocycle-based (cryptand n-decyl-[2.2.2]) ion-exchange chromatographic phase to improve the selectivity for a mixture of model analytes. We introduced an alternative internal gradient method by mixed eluent (i.e. eluents formed by combination of two alkali hydroxide with different molar ratio). The effect of binary mixed eluent (Li/Na, Li/K) on the retention behavior and peak shape of carboxylic acids are also discussed in view of the proposed theory. It was shown that the effects of binary aqueous mobile phases, held isocratically behave very similar to the step gradient mode. The "internal gradient" separation system has advantages over traditional step gradient mode. Twenty-six anions of widely varying chemical character (mono-, di-, tri-valent inorganic anions, mono-, di-, tri-valent aliphatic carboxylic acids, aromatic- and haloacetic carboxylic acids) were investigated on the cryptand-based (D222) stationary phase using different methods by LiOH, NaOH and KOH eluent. The predicted vs measured retention data are in rather good agreement. High degree of linearity was obtained for inorganic anions, multivalent carboxylic acids, and for aromatic and haloacetic acids R2 = 0.992, 0.969, and 0.980, respectively.


Assuntos
Ácidos Carboxílicos/análise , Cromatografia por Troca Iônica/métodos , Éteres Cíclicos/química , Bases de Schiff/química , Ácidos/química , Ânions/química , Ácidos Carboxílicos/isolamento & purificação , Troca Iônica
2.
J Photochem Photobiol B ; 203: 111735, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31864090

RESUMO

Complexation behavior of cyclophane amide molecular receptors towards 7,7,8,8-tetracyanoquinodimethane (TCNQ) studied. TD-B3LYP/6-31 + G(d,p) based density functional theory was employed to investigate the photophysical characteristics of the complexes obtained. Syn isomers of cyclophane amide molecular hosts show preferred conformation over other conformations. Molecular Orbital analysis indicates the electronic structure change, which reflects in the absorption spectra of the cyclophane amide-1@TCNQ, and cyclophane amide-2@TCNQ charge-transfer (CT) complexes. Binding energy studies with B3LYP-D3/6-31 + G (d,p) theory demonstrated that the more effective binding of the pyridine-2,6-dicarboxamide macrocycles than for their isophthalamide analogs. Both the CT complexes show intermolecular bifurcated hydrogen bonding (N-H(host)···N(guest)···H-N(host)) interactions (2.06 to 2.08 Å), and π(host)···π(guest) interactions (3.2 to 3.4 Å). Calculated BSSE corrected complexation energy (ΔE) be associated with the formation of the inclusion complexes in the range - 28 to -37 kJ mol-1, indicating spontaneity of host-guest complex formation in both the cases. From the calculated vibrational spectra of these complexes, the formation of inclusion complexes via N - H(host)···N(guest) and π(host)···π(guest) intermolecular interactions established by the frequency shift in the N - H vibrations. Mulliken population analysis performed to recognize the CT process and the variation in charges between the free and complex TCNQ molecules suggests the intermolecular charge transfer. This study indicates that these cyclophane amides can be a decent CT complexation host for the guests like TCNQ.


Assuntos
Teoria da Densidade Funcional , Éteres Cíclicos/química , Nitrilos/química , Piperidinas/química , Ligação de Hidrogênio , Conformação Molecular , Eletricidade Estática
3.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640154

RESUMO

Saturated oxygen heterocycles are widely found in a broad array of natural products and other biologically active molecules. In medicinal chemistry, small and medium rings are also important synthetic intermediates since they can undergo ring-opening and -expansion reactions. These applications have driven numerous studies on the synthesis of oxygen-containing heterocycles and considerable effort has been devoted toward the development of methods for the construction of saturated oxygen heterocycles. This paper provides an overview of the biological roles and synthetic strategies of saturated cyclic ethers, covering some of the most studied and newly discovered related natural products in recent years. This paper also reports several promising and newly developed synthetic methods, emphasizing 3-7 membered rings.


Assuntos
Produtos Biológicos/química , Éteres Cíclicos/síntese química , Animais , Produtos Biológicos/farmacologia , Química Farmacêutica , Avaliação Pré-Clínica de Medicamentos , Éteres Cíclicos/química , Éteres Cíclicos/farmacologia , Humanos , Estrutura Molecular , Oxigênio/química
4.
Methods Mol Biol ; 2001: 203-233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31134573

RESUMO

The pharmaceutical industry has focused mainly in the development of small-molecule entities intended for oral administration for the past decades. As a result, the majority of existing drugs address only a narrow range of biological targets. In the era of post-genomics, transcriptomics, and proteomics, there is an increasing interest on larger modulators of proteins that can span larger surfaces, access new therapeutic mechanisms of action, and provide greater target specificity. Traditional drug-like molecules developed using "rule-of-five" (Ro5) guidelines have been proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. However, natural products are known to be effective at modulating such targets, leading to a renewed focus by medicinal chemists on investigating underrepresented chemical scaffolds associated with natural products. Here we describe recent efforts toward identification of novel natural cyclopeptides and macrocycles as well as selected medicinal chemistry strategies to increase drug-like properties or further exploration of their activity.


Assuntos
Produtos Biológicos/química , Compostos Macrocíclicos/química , Peptídeos Cíclicos/química , Antraquinonas/química , Antraquinonas/uso terapêutico , Disponibilidade Biológica , Produtos Biológicos/farmacocinética , Produtos Biológicos/uso terapêutico , Química Farmacêutica , Ciclosporina/química , Ciclosporina/uso terapêutico , Ciclotídeos/química , Ciclotídeos/uso terapêutico , Daptomicina/química , Daptomicina/uso terapêutico , Depsipeptídeos/química , Depsipeptídeos/uso terapêutico , Desenho de Fármacos , Descoberta de Drogas , Éteres Cíclicos/química , Éteres Cíclicos/uso terapêutico , Gramicidina/química , Gramicidina/uso terapêutico , Lipopeptídeos/química , Lipopeptídeos/uso terapêutico , Compostos Macrocíclicos/farmacocinética , Compostos Macrocíclicos/uso terapêutico , Macrolídeos/química , Macrolídeos/uso terapêutico , Compostos Organofosforados/química , Compostos Organofosforados/uso terapêutico , Oxazóis/química , Oxazóis/uso terapêutico , Peptídeos/química , Peptídeos/uso terapêutico , Peptídeos Cíclicos/farmacocinética , Peptídeos Cíclicos/uso terapêutico , Tiazóis/química , Tiazóis/uso terapêutico , Tiazolidinas/química , Tiazolidinas/uso terapêutico , ômega-Conotoxinas/química , ômega-Conotoxinas/uso terapêutico
5.
Org Lett ; 21(8): 2615-2619, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30969776

RESUMO

Hydroxy-containing cyclic ethers react with thermally generated benzynes to produce aryl ethers. Diverse reactivity was observed. Cleavage of the cyclic ether was involved in most of the pathways. The transformations are rationalized via initial formation of oxonium ion-containing 1,3-zwitterions arising from preferential nucleophilic attack on the benzyne by the ether oxygen. Pinacol-like rearrangements, including ring expansion, to yield aldehydes or ketones and oxirane fragmentations to generate aryl enol ethers were main competing events.


Assuntos
Derivados de Benzeno/química , Compostos de Epóxi/química , Óxido de Etileno/química , Glicóis/química , Propanóis/química , Álcoois/química , Aldeídos/química , Cicloexenos/química , Éteres Cíclicos/química , Cetonas/química
6.
Org Lett ; 21(9): 3295-3298, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31013112

RESUMO

This work characterizes a previously undetected epimerization in the preparation of alkynyl diols from pentose precursors utilizing the Ohira-Bestmann reagent. Lithium trimethylsilyldiazomethane (Colvin reagent) additions to the d-ribose and d-lyxose-derived benzylidene acetals provide the respective alkynyl diol stereoisomers, without epimerization. Regioselective tungsten-catalyzed cycloisomerizations of the d-ribose- and d-lyxose-derived alkynyl diols yield rigid bicyclic pyranose glycals, confirming the stereochemical fidelity of the Colvin alkynylation process.


Assuntos
Alquinos/química , Éteres Cíclicos/síntese química , Pentoses/química , Acetais/química , Álcoois/química , Catálise , Compostos de Lítio/química , Estrutura Molecular , Ribose/química , Estereoisomerismo , Tungstênio/química
7.
J Org Chem ; 84(5): 2415-2424, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30706711

RESUMO

B(C6F5)3 enables the metal-free unprecedented substrate-controlled direct α-stereoselective synthesis of deoxyglycosides from glycals. 2,3-Unsaturated α- O-glycoside products are obtained with deactivated glycals at 75 °C in the presence of the catalyst, while 2-deoxyglycosides are formed using activated glycals that bear no leaving group at C-3 at lower temperatures. The reaction proceeds in good to excellent yields via concomitant borane activation of glycal donor and nucleophile acceptor. The method is exemplified with the synthesis of a series of rare and biologically relevant glycoside analogues.


Assuntos
Éteres Cíclicos/química , Glicosídeos/síntese química , Boranos/química , Catálise , Glicosilação , Hidrocarbonetos Fluorados/química , Estereoisomerismo
8.
J Nat Prod ; 82(1): 148-153, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30623657

RESUMO

A laboratory culture of the colonial marine alga Chrysophaeum taylorii NIES-1699 yielded a set of new bioactive chrysophaentin analogs, and their structures were determined by HRESIMS and NMR spectroscopy. Differences in the metabolites identified between cultured C. taylorii NIES-1699 and field-collected strains from the U.S. Virgin Islands revealed additional structure-activity relationships for the Gram-positive antibiotic activity of the chrysophaentins. The presence of new hemichrysophaentins and a C-C linked biphenyl analog suggest novel features of their biosynthetic pathway. Bayesian analysis of the alignment of the 18S rRNA gene places the microalga C. taylorii in the pelagophyte clade.


Assuntos
Antibacterianos/isolamento & purificação , Compostos de Bifenilo/isolamento & purificação , Microalgas/metabolismo , Antibacterianos/farmacologia , Teorema de Bayes , Compostos de Benzil , Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Éteres Cíclicos , Biologia Marinha , Relação Estrutura-Atividade
9.
Appl Microbiol Biotechnol ; 103(6): 2449-2467, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30610285

RESUMO

Cyclobutanes containing one oxygen atom in a molecule are called oxetane-containing compounds (OCC). More than 600 different OCC are found in nature; they are produced by microorganisms, and also found in marine invertebrates and algae. The greatest number of them is found in plants belonging to the genus Taxus. Oxetanes are high-energy oxygen-containing non-aromatic heterocycles that are of great interest as new potential pharmacophores with a significant spectrum of biological activities. The biological activity of OCC that is produced by bacteria and Actinomycetes demonstrates antineoplastic, antiviral (arbovirus), and antifungal activity with confidence an angiogenesis stimulator, respiratory analeptic, and antiallergic activity dominate with confidence from 81 to 99%.


Assuntos
Produtos Biológicos/química , Éteres Cíclicos/química , Antifúngicos/isolamento & purificação , Antivirais/isolamento & purificação , Organismos Aquáticos/química , Bactérias/química , Produtos Biológicos/isolamento & purificação , Cianobactérias/química , Redes e Vias Metabólicas , Plantas/química
10.
Radiat Res ; 191(2): 139-153, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30499383

RESUMO

We quantitated age-related accumulation of senescent cells in irradiated Fanconi anemia (FA) (Fanca-/- mouse cell lines in vitro, and monitored the effect of continuous administration (via drinking water) of the water-soluble radiation mitigator, MMS350, on tissues in vivo over one year after 7.5 Gy total-body irradiation (TBI). Irradiated Fanca-/- mouse bone marrow stromal cell lines showed increased numbers of beta-galactosidase- and p21-positive senescent cells compared to Fanca+/+ cell lines, which was reduced by MMS350. One week after 7.5 Gy TBI, Fanca-/- mice showed increased numbers of senescent cells in spleen compared to Fanca+/+ controls, decreased bone marrow cellularity, failure of explanted bone marrow to proliferate in vitro to form a hematopoietic microenvironment and no detectable single stromal cell cloning capacity. There was no detectable amelioration by MMS350 administration at one week. In contrast, one year post-TBI, Fanca-/- mice demonstrated fewer senescent cells in brain and spleen compared to Fanca+/+ controls. While Fanca-/- mouse bone marrow stromal cells explanted one year post-TBI still failed to proliferate in vitro, continuous oral administration of 400 µ M, MMS350 in drinking water restored explanted stromal cell proliferation. The data indicate that continuous administration of MMS350 modulated several properties of TBI-accelerated aging in Fanca-/- mice as well as control mice, and support further study of MMS350 as a modulator of radiation late effects.


Assuntos
Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Éteres Cíclicos/administração & dosagem , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos da radiação , Protetores contra Radiação/administração & dosagem , Sulfóxidos/administração & dosagem , Irradiação Corporal Total , Administração Oral , Animais , Éteres Cíclicos/farmacologia , Feminino , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Knockout , Protetores contra Radiação/farmacologia , Sulfóxidos/farmacologia , Microambiente Tumoral
11.
Molecules ; 23(12)2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30572602

RESUMO

Crystallization of tetraphosphonate cavitand Tiiii[H, CH3, CH3] in the presence of positively charged amino acids, namely arginine, lysine, or histidine, afforded host-guest complex structures. The X-ray structure determination revealed that in all three structures, the fully protonated form of the amino acid is ditopically complexed by two tetraphosphonate cavitand molecules. Guanidinium, ammonium, and imidazolium cationic groups of the amino acid side chain are hosted in the cavity of a phosphonate receptor, and are held in place by specific hydrogen bonding interactions with the P=O groups of the cavitand molecule. In all three structures, the positively charged α-ammonium groups form H-bonds with the P=O groups, and with a water molecule hosted in the cavity of a second tetraphosphonate molecule. Furthermore, water-assisted dimerization was observed for the cavitand/histidine ditopic complex. In this 4:2 supramolecular complex, a bridged water molecule is held by two carboxylic acid groups of the dimerized amino acid. The structural information obtained on the geometrical constrains necessary for the possible encapsulation of the amino acids are important for the rational design of devices for analytical and medical applications.


Assuntos
Aminoácidos/química , Arginina/química , Éteres Cíclicos/química , Histidina/química , Lisina/química , Resorcinóis/química , Ligação de Hidrogênio , Conformação Molecular
12.
Yakugaku Zasshi ; 138(12): 1537-1547, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30504670

RESUMO

We previously showed that a naturally occurring macrocyclic bis(bibenzyl) derivative, riccardin C (RC), exhibits antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), with a potency comparable to that of the clinically used drug vancomycin. Here, we synthesized a series of RC derivatives to explore the structure-activity relationships (SAR). The SAR results clearly indicated that the number and positions of the phenolic hydroxyl groups are primary determinants of the anti-MRSA activity. Pharmacological characterization of the macrocyclic bis(bibenzyl) derivatives, together with fragment compounds and their dimers, indicated that the macrocycles and the fragment compounds elicit anti-MRSA activity with different mechanism(s) of action. The macrocyclic bis(bibenzyl)s are bactericidal, while the fragment compounds are bacteriostatic, showing only weak bactericidal activity. Treatment with a macrocyclic bis(bibenzyl) derivative significantly changed the intracellular Na+ and K+ concentrations of Staphylococcus aureus, and transmission electron microscopy revealed that treated cells developed intracellular lamellar mesosomal-like structures. These results indicated that the macrocyclic compound directly damages the gram-positive bacterial membrane, resulting in increased permeability.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Desenho de Fármacos , Éteres Cíclicos/síntese química , Éteres Cíclicos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Farmacorresistência Bacteriana , Éteres Cíclicos/química , Staphylococcus aureus Resistente à Meticilina/citologia , Staphylococcus aureus Resistente à Meticilina/metabolismo , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Microscopia Eletrônica de Transmissão , Potássio/metabolismo , Sódio/metabolismo , Relação Estrutura-Atividade
13.
Yakugaku Zasshi ; 138(11): 1335-1344, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30381641

RESUMO

Marine natural products and biologically active compounds often contain cyclic ether units. Thus, regio- and stereoselective construction of these structures has long been a topic of interest in organic synthesis. This review summarizes new synthetic approaches to polycyclic ether natural products utilizing the features of chemical elements.


Assuntos
Produtos Biológicos/síntese química , Elementos , Éteres Cíclicos/síntese química , Biologia Marinha , Toxinas Marinhas/síntese química , Oxocinas/síntese química , Animais , Produtos Biológicos/química , Catálise , Química Orgânica/métodos , Éteres Cíclicos/química , Ouro , Interações Hidrofóbicas e Hidrofílicas , Toxinas Marinhas/química , Camundongos , Conformação Molecular , Fenômenos de Química Orgânica , Oxocinas/química , Rênio/química , Estereoisomerismo
14.
J Org Chem ; 83(23): 14637-14645, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30427675

RESUMO

An N-heterocyclic carbene (NHC)-catalyzed reaction of γ-substituted allenoates for the synthesis of substituted oxetanes has been developed. The method provides an approach to access substituted oxetanes in a single step and is the first example of an NHC-catalyzed formal [2+2]-annulation employing γ-substituted allenoates with trifluoromethyl ketones. Mechanistic and modeling studies provide a rationale for the divergence in reactivity observed compared to the analogous reaction using unsubstituted allenoates and inform a hypothesis to explain the observed diastereoselectivity under different reaction conditions.


Assuntos
Éteres Cíclicos/química , Metano/análogos & derivados , Catálise , Metano/química , Estrutura Molecular
15.
Molecules ; 23(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336589

RESUMO

Two synthetic protocols for the introduction of fluorine atoms into resorcinarene-based cavitands, at the lower and upper rim, respectively, are reported. Cavitand 1, bearing four fluorocarbon tails, and cavitand 2, which presents a fluorine atom on the para position of a diester phosphonate phenyl substituent, were synthesized and their complexation abilities toward the model guest sarcosine methyl ester hydrochloride were evaluated via NMR titration experiments. The effect of complexation on the 19F NMR resonance of the probe is evident only in the case of cavitand 2, where the inset of the cation-dipole and H-bonding interactions between the P=O bridges and the guest is reflected in a sizable downfield shift of the fluorine probe.


Assuntos
Calixarenos/química , Éteres Cíclicos/química , Flúor/química , Fenilalanina/análogos & derivados , Resorcinóis/química , Cátions/química , Halogenação , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Organofosfonatos/química , Fenilalanina/química , Sarcosina/análogos & derivados , Sarcosina/química
16.
Chem Soc Rev ; 47(18): 7006-7026, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30175351

RESUMO

Preventive healthcare asks for the development of cheap, precise and non-invasive sensor devices for the early detection of diseases and continuous population screening. The actual techniques used for diagnosis, e.g. MRI and PET, or for biochemical marker sensing, e.g. immunoassays, are not suitable for continuous monitoring since they are expensive and prone to false positive responses. Synthetic supramolecular receptors offer new opportunities for the creation of specific, selective and cheap sensor devices for biological sensing of specific target molecules in complex mixtures of organic substances. The fundamental challenges faced in developing such devices are the precise transfer of the molecular recognition events at the solid-liquid interface and its transduction into a readable signal. In this review we present the progress made so far in turning synthetic macrocyclic hosts, namely cyclodextrins, calixarenes, cucurbiturils and cavitands, into effective biochemical sensors and the strategies utilized to solve the above mentioned issues. The performances of the developed sensing devices based on these receptors in detecting specific biological molecules, drugs and proteins are critically discussed.


Assuntos
Anticorpos/análise , DNA/análise , Compostos Macrocíclicos/química , Preparações Farmacêuticas/análise , Proteínas/análise , Calixarenos/química , Ciclodextrinas/química , Técnicas Eletroquímicas , Éteres Cíclicos/química , Humanos , Resorcinóis/química
17.
ACS Nano ; 12(8): 8029-8036, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30028590

RESUMO

Cyclophanes are macrocyclic supramolecular hosts famous for their ability to bind atomic or molecular guests via noncovalent interactions within their well-defined cavities. In a similar way, porous crystalline networks, such as metal-organic frameworks, can create microenvironments that enable controlled guest binding in the solid state. Both types of materials often consist of synthetic components, and they have been developed within separate research fields. Moreover, the use of biomolecules as their structural units has remained elusive. Here, we have synthesized a library of organic cyclophanes and studied their electrostatic self-assembly with biological metal-binding protein cages (ferritins) into ordered structures. We show that cationic pillar[5]arenes and ferritin cages form biohybrid cocrystals with an open protein network structure. Our cyclophane-protein cage frameworks bridge the gap between molecular frameworks and colloidal nanoparticle crystals and combine the versatility of synthetic supramolecular hosts with the highly selective recognition properties of biomolecules. Such host-guest materials are interesting for porous material applications, including water remediation and heterogeneous catalysis.


Assuntos
Éteres Cíclicos/química , Ferritinas/química , Estruturas Metalorgânicas/química , Cristalização , Modelos Moleculares , Tamanho da Partícula , Porosidade , Propriedades de Superfície
18.
J Am Chem Soc ; 140(26): 8350-8356, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29939024

RESUMO

C(sp3)-H bond functionalization has emerged as a robust tool enabling rapid construction of molecular complexity from simple building blocks, and the development of asymmetric versions of this reaction creates a powerful methodology to access enantiopure sp3-rich materials. Herein, we report the stereoselective functionalization of C(sp3)-H bonds of cyclic ethers employing a photochemically active diaryliodonium salt in combination with an anionic phase-transfer catalyst. The synthetic strategy outlined herein allows for regio- and stereochemical control in the α-C-H acetalization of furans and pyrans using alcohol nucleophiles, thus providing the ability to control the configuration at the stereogenic exocyclic acetal carbon.


Assuntos
Acetais/síntese química , Éteres Cíclicos/química , Luz , Oniocompostos/química , Fosfatos/química , Acetais/química , Furanos/química , Estrutura Molecular , Piranos/química , Estereoisomerismo
19.
Biodegradation ; 29(3): 301-310, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29696449

RESUMO

Rhodococcus aetherivorans JCM 14343 can degrade 1,4-dioxane as a sole carbon and energy source. This study aimed to characterize this 1,4-dioxane degradation ability further, and assess the potential use of the strain for 1,4-dioxane removal in industrial wastewater. Strain JCM 14343 was able to degrade 1,4-dioxane inducibly, and its 1,4-dioxane degradation was also induced by tetrahydrofuran and 1,4-butanediol. The demonstration that 1,4-butanediol not only induced but also enhanced 1,4-dioxane degradation was a novel finding of this study. Although strain JCM 14343 appeared not to be an effective 1,4-dioxane degrader considering the maximum specific 1,4-dioxane degradation rate (0.0073 mg-dioxane/mg-protein/h), half saturation concentration (59.2 mg/L), and cell yield (0.031 mg-protein/mg-1,4-dioxane), the strain could degrade over 1100 mg/L of 1,4-dioxane and maintain its degradation activity at a wide range of temperature (5-40 °C) and pH (4-9) conditions. This suggests the usefulness of strain JCM 14343 in 1,4-dioxane treatment under acidic and cold conditions. In addition, 1,4-dioxane degradation experiments in the presence of ethylene glycol (EG) or other cyclic ethers revealed that 1,4-dioxane degradation by strain JCM 14343 was inhibited in the presence of other cyclic ethers, but not by EG, suggesting certain applicability of strain JCM 14343 for industrial wastewater treatment.


Assuntos
Dioxanos/metabolismo , Rhodococcus/metabolismo , Biodegradação Ambiental/efeitos dos fármacos , Éteres Cíclicos/farmacologia , Etilenoglicol/farmacologia , Concentração de Íons de Hidrogênio , Cinética , Rhodococcus/enzimologia , Rhodococcus/crescimento & desenvolvimento , Temperatura
20.
Nat Chem ; 10(5): 540-548, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29610465

RESUMO

New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein-protein interactions. Here, we report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)-H arylation reactions. Easily accessible linear peptide precursors of simple and versatile design can be selectively cyclized at the side chains of either aromatic or modified non-aromatic amino acid units to form various cyclophane-braced peptide cycles. This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures. Preliminary cell proliferation screening of the pilot library revealed a potent lead compound with selective cytotoxicity toward proliferative Myc-dependent cancer cell lines.


Assuntos
Carbono/química , Éteres Cíclicos/química , Hidrogênio/química , Compostos Macrocíclicos/química , Paládio/química , Peptídeos/química , Catálise , Linhagem Celular Tumoral , Ciclização , Teoria da Densidade Funcional , Humanos
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