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991.
Özlen Güzel Alfonso Maresca Andrea Scozzafava Aydın Salman Alexandru T. Balaban Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2009,19(11):2931-2934
A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents. 相似文献
992.
Özlen Güzel Alessio Innocenti Andrea Scozzafava Aydın Salman Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2009,19(12):3170-3173
A series of aromatic/heterocyclic sulfonamides incorporating phenyl(alkyl), halogenosubstituted-phenyl- or 1,3,4-thiadiazole-sulfonamide moieties and thienylacetamido; phenacetamido- and pyridinylacetamido tails were prepared and assayed as inhibitors of cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I, II and VII. The new compounds showed moderate inhibition of the two ubiquitous isoforms I and II (KIs of 50–390 nM) and excellent inhibitory activity against the brain associated hCA VII (KIs in the range of 4.7–8.5 nM). Isoform VII highly selective inhibitors are being detected for the first time, with selectivity ratios for inhibiting CA VII over CA II of 11–75, and for inhibiting CA VII over CA I of 10–49, which may be useful for understanding the role of CA VII in epileptogenesis and other physiologic processes. 相似文献
993.
Extracellular Matrix Stiffness and Architecture Govern Intracellular Rheology in Cancer 总被引:2,自引:0,他引:2
Little is known about the complex interplay between the extracellular mechanical environment and the mechanical properties that characterize the dynamic intracellular environment. To elucidate this relationship in cancer, we probe the intracellular environment using particle-tracking microrheology. In three-dimensional (3D) matrices, intracellular effective creep compliance of prostate cancer cells is shown to increase with increasing extracellular matrix (ECM) stiffness, whereas modulating ECM stiffness does not significantly affect the intracellular mechanical state when cells are attached to two-dimensional (2D) matrices. Switching from 2D to 3D matrices induces an order-of-magnitude shift in intracellular effective creep compliance and apparent elastic modulus. However, for a given matrix stiffness, partial blocking of β1 integrins mitigates the shift in intracellular mechanical state that is invoked by switching from a 2D to 3D matrix architecture. This finding suggests that the increased cell-matrix engagement inherent to a 3D matrix architecture may contribute to differences observed in viscoelastic properties between cells attached to 2D matrices and cells embedded within 3D matrices. In total, our observations show that ECM stiffness and architecture can strongly influence the intracellular mechanical state of cancer cells. 相似文献
994.
A rapid, simple in vitro test system for high-throughput screening of peroxisome proliferator-activated receptor (PPAR) γ agonists would be of interest for testing new antidiabetic drugs, alternative medicine, or environmental samples. A yeast two-hybrid assay based on the ligand-dependent recruitment of the coactivator CBP (CREB-binding protein) was constructed. In this system PPARγ was constitutively activated and the signal was not further increased significantly by adding agonists. In yeast we identified oleic acid as a putative endogenous ligand. Furthermore yeasts seem to lack regulatory mechanisms present in mammalian cells. Mammalian systems are an alternative for screening PPARγ agonists. 相似文献
995.
An amperometric lactate biosensor was developed based on a conducting polymer, poly-5,2′-5′,2′′-terthiophene-3′-carboxylic acid (pTTCA), and multiwall carbon nanotube (MWNT) composite on a gold electrode. Lactate dehydrogenase (LDH) and the oxidized form of nicotinamide adenine dinucleotide (NAD+) were subsequently immobilized onto the pTTCA/MWNT composite film. The modified electrode was characterized by quartz crystal microbalance (QCM), scanning electron microscopy (SEM), and electrochemical experiments. The detection signal was amplified by the pTTCA/MWNT assembly onto which a sufficient amount of enzyme was immobilized and stabilized by the covalent bond formation between the amine groups of enzyme and the carboxylic acid groups of the pTTCA/MWNT film. Experimental parameters affecting the sensor responses, such as applied potential, pH, and temperature, were assessed and optimized. Analytical performances and dynamic ranges of the sensor were determined, and the results showed that the sensitivity, stability, and reproducibility of the sensor improved significantly using pTTCA/MWNT composite film. The calibration plot was linear (r2 = 0.9995) over the range of 5 to 90 μM. The sensitivity was approximately 0.0106 μA/μM, with a detection limit of 1 μM, based on a signal/noise ratio of 3. The applicability of the sensor for the analysis of l-lactate concentration in commercial milk and human serum samples was demonstrated successfully. 相似文献
996.
Evolution of geminiviruses and their satellites 总被引:1,自引:0,他引:1
Muhammad Shah Nawaz-ul-Rehman 《FEBS letters》2009,583(12):1825-113
Geminiviruses and their satellites have circular single stranded DNA genomes, infecting many crops and weeds across the globe. To successfully invade new hosts, break host resistance, move virus particles within and between plants, geminiviruses and their satellites have evolved a coordinated network of protein interactions, showing a possible evolutionary path. Humans have played an important role in the last century to promote the emergence of many geminivirus diseases, thereby impacting their evolution. The greatest molecular diversity of geminiviruses and their satellites resides in Southeast Asia revealing a possible center of origin. This minireview leads us to a possible general grand scheme of their evolution. 相似文献
997.
Kang SM Joo GJ Hamayun M Na CI Shin DH Kim HY Hong JK Lee IJ 《Biotechnology letters》2009,31(2):277-281
Plant growth-promoting rhizobacteria with gibberellins (GA)-producing potential were isolated from soil and screened for plant
growth promotion. A new strain, Acinetobacter calcoaceticus SE370, produced extracellular GA and also had phosphate solubilising potential. It produced 10 different gibberellins, including
the bioactive GA1, GA3 and GA4 which were at, respectively, 0.45, 6.2 and 2.8 ng/100 ml. The isolate solubilised tricalcium phosphate and lowered pH of
the medium during the process. Culture filtrates of the organism after growth on broth promoted growth of cucumber, Chinese
cabbage and crown daisy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
998.
Khan SA Hamayun M Kim HY Yoon HJ Seo JC Choo YS Lee IJ Kim SD Rhee IK Kim JG 《Biotechnology letters》2009,31(2):283-287
Plant growth-promoting endophytic fungi with gibberellin-producing ability were isolated from the roots of Carex kobomugi Ohwi, a common sand-dune plant, and bioassayed for plant growth-promotion. A new strain, Arthrinium phaeospermum KACC43901, promoted growth of waito-c rice and Atriplex gemelinii. Analysis of its culture filtrate showed the presence of bioactive GA1 (0.5 ng/ml), GA3 (8.8 ng/ml), GA4 (4.7 ng/ml) and GA7 (2.2 ng/ml) along with physiologically inactive GA5 (0.4 ng/ml), GA9 (0.6 ng/ml), GA12 (0.4 ng/ml), GA15 (0.4 ng/ml), GA19 (0.9 ng/ml) and GA24 (1.8 ng/ml). The fungal isolate was identified through sequence homology and phylogenetic analysis of 18S rDNA (internal
transcribed region).
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
999.
Hassan Rashidi Muhammad T. Akhtar Frank van der Kooy Robert Verpoorte Wouter A. Duetz 《Applied and environmental microbiology》2009,75(22):7135-7141
The microbial biotransformation of Δ9-tetrahydrocannabinol was investigated using a collection of 206 alkane-degrading strains. Fifteen percent of these strains, mainly gram-positive strains from the genera Rhodococcus, Mycobacterium, Gordonia, and Dietzia, yielded more-polar derivatives. Eight derivatives were produced on a mg scale, isolated, and purified, and their chemical structures were elucidated with the use of liquid chromatography-mass spectrometry, 1H-nuclear magnetic resonance (1H-NMR), and two-dimensional NMR (1H-1H correlation spectroscopy and heteronuclear multiple bond coherence). All eight biotransformation products possessed modified alkyl chains, with hydroxy, carboxy, and ester functionalities. In a number of strains, β-oxidation of the initially formed C5 carboxylic acid led to the formation of a carboxylic acid lacking two methylene groups.Δ9-Tetrahydrocannabinol (Δ9-THC) is the decarboxylated product of the corresponding Δ9-THC acid, the major cannabinoid present in the cannabis plant (Cannabis sativa L., Cannabaceae). This compound is officially registered as a drug for the stimulation of appetite and antiemesis in patients under chemotherapy and human immunodeficiency virus therapy regimens. Other biological activities ascribed to this compound include lowering intraocular pressure in glaucoma, acting as an analgesic for muscle relaxation, immunosuppression, sedation, bronchodilation, and neuroprotection (11).Δ9-THC and many of its derivatives are highly lipophilic and poorly water soluble. Calculations of the n-octanol/water partition coefficient (Ko/w) of Δ9-THC at neutral pH vary between 6,000, using the shake flask method (15), and 9.44 × 106, by reverse-phase high-performance liquid chromatography estimation (19). The poor water solubility and high lipophilicity of cannabinoids cause their absorption across the lipid bilayer membranes and fast elimination from blood circulation. In terms of the “Lipinsky rule of 5” (14), the high lipophilicity of cannabinoids hinders the further development of these compounds into large-scale pharmaceutical products.To generate more water-soluble analogues, one can either apply de novo chemical synthesis (as, e.g., in reference 16) or modify naturally occurring cannabinoids, e.g., by introducing hydroxy, carbonyl, or carboxy groups. Chemical hydroxylation of compounds such as cannabinoids is difficult (Δ9-THC is easily converted into Δ8-THC under mild conditions), and therefore microbial biotransformation of cannabinoids is potentially a more fruitful option to achieve this goal.So far, studies on biotransformation of Δ9-THC were mainly focused on fungi, which led to the formation of a number of mono- and dihydroxylated derivatives. Previous reports on the biotransformation of cannabinoids by various microorganisms are summarized in Table Table1.1. The aim of the present study was to test whether bacterial strains are capable of transforming Δ9-THC into new products (with potentially better pharmaceutical characteristics) at a higher yield and specificity than previously found for fungal strains. For this purpose, we have chosen to use a collection of alkane-degrading strains, since it was shown in previous studies (8, 18, 20) that alkane oxygenases often display a broad substrate range. Production of novel cannabinoid derivatives that might have interesting pharmacological activities was another objective of this project.
Open in a separate windowaCBD, cannabidiol; CBN, cannabinol. 相似文献
TABLE 1.
Previous biotransformation experiments conducted using various microorganisms to transform cannabinoidsCannabinoid(s)a | Microorganism(s) used | No. of transformed products | Reference |
---|---|---|---|
Δ9-THC | Cunninghamella blakesleeana | 6 | 3 |
Δ8-THC | Pellicularia filamentosa | 4 | 21 |
Δ8-THC | Streptomyces lavendulae | 4 | 21 |
Δ6a,10a-THC | 400 cultures (soil microorganisms) | Various | 1 |
Nabilone | 400 cultures (soil microorganisms) | Various | 1 |
Δ6a,10a-THC | 358 cultures containing bacteria, actinomycetes, and molds | 3 | 10 |
Δ9-THC, Δ8-THC, CBD, CBN | Syncephalastrum racemosum, Mycobacterium rhodochrous | Various | 17 |
Δ9-THC | Chaetomium globosum | 3 | 7 |
Δ9-THC | 51 fungal strains | 8 | 4 |
Nabilone | Microbes | Various | 2 |
Δ9-THC | Fusarium nivale, Gibberella fujikuroi, and Thamnidium elegans | 8 | 5 |
1000.
Ibtesam A. Saeed S. Salman Ashraf 《International journal of biological macromolecules》2009,45(3):236-241
Green fluorescent protein (GFP) is an unusually stable fluorescent protein that belongs to a family of related auto-fluorescent proteins (AFPs). These AFPs have been generated from jellyfish GFP by mutating the amino acids in the chromophore or its vicinity. Variants that emit light in the blue region (Blue Fluorescent Protein, BFP), red region, or yellow region are readily available and are widely used in diverse applications. Previously, we had used fluorescence spectroscopy to study the effect of pH on the denaturation of GFP with SDS, urea, and heat. Surprisingly, we found that SDS, urea or heat, did not have any significant effect on the fluorescence of GFP at pH 7.5 or 8.5, however, at pH 6.5, the protein lost all fluorescence within a very short period of time. These results suggested that GFP undergoes a structural/stability shift between pH 6.5 and 7.5, with the GFP structure at pH 6.5 being very sensitive to denaturation by SDS, urea, and heat. In the present study, we wanted to explore whether the stability or structure of the closely related BFP is also pH dependent. As expected, we found heat-induced denaturation and renaturation of BFP to be pH dependent, very much like GFP. However, when exposed to other denaturants like urea/heat or SDS we found BFP to behave very differently than GFP. Unlike GFP, which at pH 8.5 and 7.5 is very resistant to SDS-induced denaturation, BFP readily lost about 20% of its fluorescence at pH 8.5 and about 60% fluorescence at pH 7.5. Also, our denaturation and renaturation studies show that under certain conditions, BFP is more stable than GFP, such that under conditions where GFP is completely denatured, BFP still retained significant fluorescence. Taken together, our preliminary results show that despite being very similar in both amino acid sequences and overall structures, there may be subtle and important structural/conformational differences between BFP and GFP. 相似文献