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291.
Anthony Bertucci Alessio Innocenti Didier Zoccola Andrea Scozzafava Sylvie Tambutté Claudiu T. Supuran 《Bioorganic & medicinal chemistry》2009,17(14):5054-5058
The inhibition of a newly cloned coral carbonic anhydrase (CA, EC 4.2.1.1) has been investigated with a series of sulfonamides, including some clinically used derivatives (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and sulpiride, or indisulam, a compound in clinical development as antitumor drug), as well as the sulfamate antiepileptic topiramate. Some simple amino-/hydrazine-/hydroxy-substituted aromatic/heterocyclic sulfonamides have also been included in the study. All types of activity have been detected, with low potency inhibitors (KIs in the range of 163–770 nM), or with medium potency inhibitors (KIs in the range of 75.1–105 nM), whereas ethoxzolamide, several clinically used sulfonamides and heterocyclic compounds showed stronger potency, with KIs in the range of 16–48.2 nM. These inhibitors may be useful to better understand the physiological role of the Stylophora pistillata CA (STPCA) in corals and its involvement in biomineralisation in this era of global warming. 相似文献
292.
T. Abdülkadir Coban Şükrü Beydemir İlhami Gücin Deniz Ekinci Alessio Innocenti Daniela Vullo Claudiu T. Supuran 《Bioorganic & medicinal chemistry》2009,17(16):5791-5795
Sildenafil citrate, a phosphodiesterase-5 (PDE5) inhibitor widely used for the treatment of erectile dysfunction was investigated for its interaction with the zinc-enzyme carbonic anhydrase (CA, EC 4.2.1.1), as it has in its molecule a piperazine moiety also found in some CA activators (CAAs). Sildenafil was a potent, low micromolar activator of several CA isozymes, such as CA I, VA and VI (KAs in the range of 1.08–6.54 μM), and activated slightly less the isoforms CA III, IV and VA (KAs of 13.4–16.8 μM). CA isozymes II, IX, XIII and XIV showed activation constants in the range of 27.5–34.0 μM, whereas the least activated isoforms were CA VII and XII (KAs of 72.9–73.0 μM). Sildenafil citrate was also given orally to Sprague-Dawley rats at 1 mg/kg body weight. Red blood cell CA activity was inhibited in the treated animals at 3–5 h post-administration (in the range of 60–85%), probably due to NO/nitrite formed by PDE5 inhibition or by another, unknown mechanism. Whether CA activation by sildenafil has clinical consequences in humans is beyond the scope of the present work and warrants further studies. 相似文献
293.
294.
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
295.
Alessio Innocenti Mika Hilvo Seppo Parkkila Andrea Scozzafava Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2009,19(13):3430-3433
An activation study of the membrane-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform XV with a series of natural and non-natural amino acids and aromatic/heterocyclic amines is reported. Murine CA XV was strongly activated by some amino acids (d-Phe, l-/d-DOPA, d-Trp, l-Tyr) and amines (dopamine, serotonin, l-adrenaline and 4-(2-aminoethyl)-morpholine) with activation constants in the range of 4.0–9.5 μM. l-/d-His, l-Phe, histamine and several other heterocyclic amines showed less efficient activation (KAs in the range of 11.6–33.4 μM). The activation profile of CA XV is quite different from that of the cytosolic isoforms CA I and II or the membrane-associated CA IV. All mammalian isoforms CA I–XV are thus characterized for their interaction with this set of amino acid and amine activators, some of which are biogenic amines or neurotransmitters present in sufficiently high amounts in various tissues for exerting significant biologic responses. 相似文献
296.
Alessio Mengoni Francesco Pini Li-Nan Huang Wen-Sheng Shu Marco Bazzicalupo 《Microbial ecology》2009,58(3):660-667
Bacteria associated with tissues of metal-hyperaccumulating plants are of great interest due to the multiple roles they may
play with respect to plant growth and resistance to heavy metals. The variability of bacterial communities associated with
plant tissues of three populations of Alyssum bertolonii, a Ni hyperaccumulator endemic of serpentine outcrops of Central Italy, was investigated. Terminal-restriction fragment length
polymorphism (T-RFLP) analysis of bacterial 16S rRNA genes was applied to DNA extracted from leaf tissues of 30 individual
plants from three geographically separated serpentine outcrops. Moreover, T-RFLP fingerprinting was also performed on DNA
extracted from the same soils from which the plants were collected. Fifty-nine unique terminal-restriction fragments (TRFs)
were identified, with more than half of the taxonomically interpreted TRFs assigned to Alpha- and Gamma-Proteobacteria and Clostridia. Data were then used to define the extent of variation of bacterial communities due to single plants or to
plant populations. Results indicated a very high plant-by-plant variation of leaf-associated community (more than 93% of total
variance observed). However, a core (numerically small) of plant-specific TRFs was found. This work demonstrates that plant-associated
bacterial communities represent a large reservoir of biodiversity and that the high variability existing between plants, even
from the same population, should be taken into account in future studies on association between bacteria and metal-hyperaccumulating
plants. 相似文献
297.
Giampaolo Barone Angela Ruggirello Alessio Terenzi 《Journal of inorganic biochemistry》2009,103(5):731-737
The interaction of native calf thymus DNA with the cationic Ni(II) complex of 5-triethyl ammonium methyl salicylidene ortho-phenylendiimine (NiL2+), in 1 mM Tris-HCl aqueous solutions at neutral pH, has been monitored as a function of the metal complex-DNA molar ratio by UV absorption spectrophotometry, circular dichroism (CD) and fluorescence spectroscopy. The dramatic modification of the DNA CD spectrum, the appearance of a broad induced CD band in the range 350-400 nm, the strong increase of the DNA melting temperature (Tm) and the fluorescence quenching of ethidium bromide-DNA solutions, in the presence of increasing amounts of the NiL2+ metal complex, support the existence of a tight intercalative interaction of NiL2+ with DNA, analogous to that recently reported for both ZnL2+ and CuL2+. The intrinsic binding constant (Kb) and the interaction stoichiometry (s), determined by UV spectrophotometric titration, are equal to 4.3 × 106 M−1 and 1.0 base pair per metal complex, respectively. Interestingly, the value of Kb is slightly higher and 10 times higher than that relative to the CuL2+-DNA and the ZnL2+-DNA systems, respectively. Speculations can be performed to rationalize the observed trend, on the basis of the electronic and geometrical structures of the three complexes of the same ligand. Analogously to what previously observed for CuL2+, the shape of the CD of the NiL2+-DNA system at NiL2+-DNA molar ratios higher than 0.5 is indicative of the formation of supramolecular aggregates in solutions, as a possible consequence of the electrostatic interaction between the cationic complex and the negatively charged phosphate groups of DNA. 相似文献
298.
Cheryl I. Champion Valerie A. Kickhoefer Guangchao Liu Raymond J. Moniz Amanda S. Freed Liisa L. Bergmann Dana Vaccari Sujna Raval-Fernandes Ann M. Chan Leonard H. Rome Kathleen A. Kelly 《PloS one》2009,4(4)
Background
Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication.Methodology/Principal Findings
We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants.Conclusions/Significance
Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as “smart adjuvants” for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation. 相似文献299.
Roscioli E Bolognesi A Guarguaglini G Lavia P 《Biochemical Society transactions》2010,38(6):1709-1714
Roles of the GTPase Ran in cell life and division rely on a largely conserved mechanism, i.e. Ran's ability to interact with transport vectors. Modes of control of downstream factors, however, are diversified at particular times of the cell cycle. Specificity and fine-tuning emerge most clearly during mitosis. In the present article, we focus on the distinction between global mitotic control by the chromosomal Ran gradient and specific spatial and temporal control operated by localized Ran network members at sites of the mitotic apparatus in human cells. 相似文献