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- ItemSomente MetadadadosAntiplasmodial activity study of angiotensin II via Ala scan analogs(Wiley-Blackwell, 2014-08-01) Silva, Adriana Farias; Bastos, Erick Leite; Torres, Marcelo Der Torossian; Costa-da-Silva, Andre Luis; Ioshino, Rafaella Sayuri; Capurro, Margareth Lara; Alves, Flavio Lopes [UNIFESP]; Miranda, Antonio [UNIFESP]; Fischer Vieira, Renata de Freitas [UNIFESP]; Oliveira, Vani Xavier; Universidade Federal do ABC (UFABC); Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid-phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide-capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. the Ala screening data indicates that the replacement of either the Ile(5) or the His(6) residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala(6)]-AII (79%), and [Ala(5)]-AII (75%). Analogs [Ala(3)]-AII, [Ala(1)]-AII, and AII-NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala(8)]-AII, [Ala(7)]-AII, [Ala(4)]-AII, and [Ala(2)]-AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a beta-fold conformation in different solutions. All AII analogs, except [Ala(4)]-AII and [Ala(8)]-AII, show contractile responses and interact with the AT(1) receptor, [Ala(5)]-AII and [Ala(6)]-AII. in conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds. Copyright (C) 2014 European Peptide Society and John Wiley & Sons, Ltd.
- ItemSomente MetadadadosDivalent metal requirements for catalysis and stability of the RNA triphosphatase from Trypanosoma cruzi(Elsevier B.V., 2006-11-01) Kikuti, Carlos Massayuki; Tersariol, Ivarne Luis S.; Schenkman, Sergio; Universidade Federal de São Paulo (UNIFESP); Univ Mogi CruzesRNA triphosphatases act in the first step of the mRNA capping process, removing the gamma-phosphoryl group from the 5' end of nascent RNA. A metal-dependent catalysis is found in the enzymes from trypanosomes and several other lower eukaryotes. This contrasts with the cysteine-dependent activity of the corresponding enzymes of mammals, a difference that points to these enzymes as potential targets for drug design. This work describes the identification, expression, purification, enzyme kinetics, and the role of divalent metal in the ATPase activity of the RNA triphosphatase from Trypanosoma cruzi, the agent of Chagas' disease, and compares it with the previously characterized enzyme from Trypanosoma brucei. Sequence similarity of the T cruzi enzyme with the RNA triphosphatase of Saccharomyces cerevisiae indicates that a tunnel domain containing the divalent metal forms its active site. Based on enzyme kinetics, circular dichroism, and intrinsic fluorescence analysis, a kinetic mechanism for the ATPase activity of the T cruzi tunnel triphosphatase is proposed. A single metal is sufficient to interact with the enzyme through the formation of a productive MnATP-enzyme complex, while free ATP inhibits activity. Manganese is also required for the tunnel stability of the T cruzi enzyme, while the T brucei homologue remains stable in the absence of metal, as shown for other triphosphatases. These findings may be useful to devise specific triphosphatase inhibitors to the T cruzi enzyme. (c) 2006 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Innovative low temperature plasma approach for deposition of alumina films(ABM, ABC, ABPol, 2014-12-01) Battaglin, Felipe Augusto Darriba; Hosokawa, Ricardo Shindi; Cruz, Nilson Cristino Da; Caseli, Luciano [UNIFESP]; Rangel, Elidiane Cipriano; Silva, Tiago Fiorini Da; Tabacniks, Manfredo Harri; Universidade Estadual Paulista (UNESP); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Alumina films were deposited from a new plasma method using aluminum acetylacetonate (AAA) powder as precursor. The AAA was sputtered in argon and oxygen plasma mixtures. It was investigated the effect of the oxygen proportion (O2%) on the properties of the coatings. Deposition rate was derived from the layer height measured by profilometry. The elemental composition and molecular structure of the films were determined by Rutherford backscattering and infrared spectroscopies, respectively. Grazing incidence X-ray diffraction was used to investigate the microstructure of the films while hardness was determined by nanoindentation technique. Inspections on the surface morphology and on the film composition were conducted associating scanning electron microscopy and energy dispersive spectroscopy. Incorporation of oxygen affects the plasma kinetics and consequently the properties of the coatings. As moderated concentrations of oxygen (< 25%) are added, the structure is predominantly organic containing stoichiometric amorphous alumina. On the other hand, as high O2% (> 25%) are incorporated, the structure become rich in metallic aluminum with carbon rising at low proportions. The deposited layer is not homogeneous in thickness once the chemical composition of the precursor is changed by the action of the reactive oxygen plasma. Oxygen ablation on the film surface also contributes to the lack of homogeneity of the structure, especially as high oxygen proportions are imposed. Hardness data (0.5-2.0 GPa) corroborated the idea of an amorphous structure. Based on the results presented here it was possible to identify the oxygen concentration in the plasma atmosphere which mostly removed organics while preserving the stoichiometric alumina precipitation, subject of great relevance as one considers the reduction in the energy necessary for the creation of fully oxide coatings.
- ItemSomente MetadadadosA minor beta-structured conformation is the active state of a fusion peptide of vesicular stomatitis virus glycoprotein(Wiley-Blackwell, 2008-04-01) Sarzedas, Carolina G.; Lima, Carla S.; Juliano, Maria A. [UNIFESP]; Juliano, Luiz [UNIFESP]; Valente, Ana Paula; Da Poian, Andrea T.; Almeida, Fabio C. L.; Universidade Federal do Rio de Janeiro (UFRJ); Universidade Federal de São Paulo (UNIFESP)Entry of enveloped animal viruses into their host cells always depends on a step of membrane fusion triggered by conformational changes in viral envelope glycoproteins. Vesicular stomatitis virus (VSV) infection is mediated by virus spike glycoprotein G, which induces membrane fusion at the acidic environment of the endosomal compartment. in a previous work, we identified a specific sequence in the VSV G protein, comprising the residues 145-164, directly involved in membrane interaction and fusion. in the present work we studied the interaction of pep[145-164] with membranes using NMR to solve the structure of the peptide in two membrane-mimetic systems: SDS micelles and liposomes composed of phosphatidylcholme and phosphatidylserine (PC: PS vesicles). the presence of medium-range NOEs showed that the peptide has a tendency to form N- and C-terminal helical segments in the presence of SDS micelles. Analysis of the chemical shift index indicated helix-coil equilibrium for the C-terminal helix under all conditions studied. At pH 7.0, the N-terminal helix also displayed a helix-coil equilibrium when pep[145-164] was free in solution or in the presence of PC: PS. Remarkably, at the fusogenic pH, the region of the N-terminal helix in the presence of SDS or PC: PS presented a third conformational species that was in equilibrium with the helix and random coil. the N-terminal helix content decreases pH and the minor P-structured conformation becomes more prevalent at the fusogenic pH. These data point to a P-conformation as the fusogenic active structure-which is in agreement with the X-ray structure, which shows a P-hairpin for the region corresponding to pep[145-164]. Copyright (c) 2007 European Peptide Society and John Wiley & Sons, Ltd.
- ItemSomente MetadadadosMolecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses(Elsevier B.V., 2006-09-01) Costa-Neto, Claudio M.; Parreiras-e-Silva, Lucas T.; Ruller, Roberto; Oliveira, Eduardo B.; Miranda, Antonio; Oliveira, Laerte; Ward, Richard J.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to cIF5A has been reported in the literature. the discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. in this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance. (c) 2006 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosA novel heparan sulphate with high degree of N-sulphation and high heparin cofactor-II activity from the brine shrimp Artemia franciscana(Elsevier B.V., 2000-03-16) Chavante, S. F.; Santos, E. A.; Oliveira, F. W.; Guerrini, M.; Torri, G.; Casu, B.; Dietrich, C. P.; Nader, H. B.; Universidade Federal de São Paulo (UNIFESP); Univ Fed Rio Grande Norte; Ist Chim & Biochim G RonzoniWith the aid of heparinase and heparitinases from Flavobacterium heparinum and C-13 and H-I NMR spectroscopy it was shown that the heparan sulphate isolated from the brine shrimp Artemia franciscana exhibits structural features intermediate between those of mammalian heparins and heparan sulphates. These include an unusually high degree of N-sulphation with corresponding very low degree of N-acetylation), a relatively high content of iduronic acid residues (both unsulphated and 2-O-sulphated) and a relatively low degree of 6-O-sulphation of the glucosamine residues. the major sequences (glucuronic acid-->N-sulphated glucosamine and glucuronic acid--> N,6-disulphated glucosamine) are most probably arranged in blocks. Although exhibiting negligible anticlotting activity in the APTT and anti-factor Xa assays the A. franciscana heparan sulphate has a high heparin cofactor-II activity (about 1/3 that of heparin). (C) 2000 Elsevier Science B.V. All rights reserved.