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Mariano Casu

Publications and source records attributed to Mariano Casu.

12 recordsLinked to original sources
PubMed2006

Structure-function relationship in a variant hemoglobin: a combined computational-experimental approach.

Our study examines the functional and structural effects of amino acid substitution in the distal side of beta-chains of human Hb Duarte (alpha(2)beta(2)(62Ala-->Pro)). We have compared the functional properties of the purified Hb Duarte with those of HbA, and through proton NMR and molecular dynamics simulations we have investigated their tertiary and quaternary structures. The variant exhibits an increased oxygen affinity with a normal Hill coefficient and Bohr effect. The abnormal function of Hb Duarte is attributed to the presence of a proline residue at the beta62 position, since the functional properties of another Hb variant in the same position, Hb J-Europa (beta(62Ala-->Asp)), have been described as normal. Thereafter (1)H-NMR studies have shown that the beta62 Ala-->Pro substitution causes structural modifications of the tertiary structure of the beta globins, leaving the quaternary structure unaltered. These results have been confirmed by extensive all-atom molecular dynamics simulations. All these findings lead to the conclusion that the beta62 Ala-->Pro substitution produces a destabilization of the E-helix extending downward to the CD corner. Particularly, a cavity near the distal histidine of the beta-chains, connecting the heme pocket to the solvent, is affected, altering the functional properties of the protein molecule.

Amino Acid Sequence↗
PubMed2006

An unexpected formation of the spectroscopic Cu(I)-semiquinone radical by xenon-induced self-catalysis of a copper quinoprotein.

Plant copper/quinone amine oxidases are homodimeric enzymes containing Cu(II) and a quinone derivative of a tyrosyl residue (2,4,5-trihydroxyphenylalanine, TPQ) as cofactors. These enzymes catalyze the oxidative deamination of primary amines by a classical ping-pong mechanism, i.e. two distinct half-reactions, enzyme reduction by substrate followed by its re-oxidation by molecular oxygen. In the first half-reaction two forms of the reduced TPQ have been observed, the colorless Cu(II)-aminoquinol and the yellow Cu(I)-semiquinolamine radical so that this enzyme may be referred to as a "protein-radical enzyme". The interaction of xenon, in aqueous solutions, with the copper/TPQ amine oxidase from lentil (Lens esculenta) seedlings has been investigated by NMR and optical spectroscopy. NMR data indicate that xenon binds to the protein. Under 10 atm gaseous xenon and in the absence of substrates more than 60% native enzyme is converted into Cu(I)-semiquinolamine radical species, showing for the first time that both monomers in the dimer can generate the radical. Under the same experimental conditions the copper-free lentil enzyme is able to generate an intermediate absorbing at about 360 nm, which is assigned to the product Schiff base quinolaldimine which, to the best of our knowledge, has never been observed during the catalytic mechanism of plant amine oxidases. A possible role of the lysine residue responsible for the formation of Cu(I)-semiquinolamine and quinolaldimine, is proposed.

Amine Oxidase (Copper-Containing)↗
PubMed2006

Cytotoxic diacetylenic spiroketal enol ethers from Plagius flosculosus.

Three new diacetylenic spiroketal enol ethers named flosculins A (1), B (2), and C (3), along with five known compounds (4-8) of the same structural class, were isolated from the leaves of Plagius flosculosus. The structures were deduced by extensive 1D and 2D NMR spectroscopy and mass spectrometry. All isolated compounds exhibited significant cytotoxic activity against leukemia cells (Jurkat T and HL-60). Compounds 5-8 induced apoptosis in HL-60 cells with corresponding IC(50) values ranging from 4 to 6 microM.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and computational study.

The methanol extract from Hypericum hircinum leaves exhibited in vitro inhibition of monoamine oxidases (MAO). Bioassay-guided fractionation led to the isolation of quercetin and five compounds identified for the first time from H. hircinum. Quercetin was the only compound with a selective inhibitory activity against MAO-A, with an IC50 value of 0.010 microM. To explain MAO selective inhibition at the molecular level, a computational study was carried out by conformational search and docking techniques using recently determined crystallographic models of both enzymatic isoforms. An in vivo study in mice was carried out using the forced swimming test in order to elucidate the behavioral effects of quercetin.

Animals↗
PubMed2005

Stability of luminescent trivalent cerium in silica host glasses modified by boron and phosphorus.

Ce-doped borosilicate (BSG), phosphosilicate (PSG), and borophosphosilicate (BPSG) glasses (B:P:Si molar ratios 8:0:92, 0:8:92, and 8:8:84; Ce:Si molar ratio 1 x 10(-)(4) to 1 x 10(-)(2)) were prepared by the sol-gel method. High-resolution transmission electron microscopy (HRTEM), (31)P, (29)Si, and (11)B magic angle spinning nuclear magnetic resonance (MAS NMR), electron paramagnetic resonance (EPR), and UV-vis absorption investigations demonstrated that, in PSG and BPSG, Ce(3+) ions interact with phosphoryl, [O=PO(3/2)], metaphosphate, [O=PO(2/ 2)O](-), and pyrophosphate, [O=PO(1/2)O(2)](2)(-), groups, linked to a silica network. This inhibits both CeO(2) segregation and oxidation of isolated Ce(3+) ions to Ce(4+), up to Ce:Si = 5 x 10(-)(3). In BSG, neither trigonal [BO(3/2)] nor tetrahedral [BO(4/2)](-) boron units coordinate cerium; thus, Ce(3+) oxidation occurs even at Ce:Si = 1 x 10(-)(4), as in pure silica glass (SG). The homogeneous rare-earth dispersion in the host matrix and the stabilization of the Ce(3+) oxidation state enhanced the intensity of the photoluminescence emission in PSG and BPSG with respect to BSG and SG. The energy of the Ce(3+) emission band in PSG and BPSG matrixes agrees with the phosphate environment of the rare earth.

Absorption↗
PubMed2005

New cytotoxic prenylated isoflavonoids from Bituminaria morisiana.

Using cytotoxicity against KB cancer cells as a lead, bioguided-fractionation of the petroleum ether and ethyl acetate extracts of Bituminaria morisiana leaves led to the isolation of two new pterocarpans, namely 3,9-dihydroxy-4-(3,3-dimethylallyl) [6a R, 11a R]-pterocarpan, 3-hydroxy-4-(3,3-dimethylallyl)-4'',5''-dehydropyrano[8,9:2'',3''][6a R,11a R]-pterocarpan and one new isoflavone identified as 4',5''-dihydroxy-6''-methoxy-4'',4''-dimethyl-4'',5''-dihydro-6'' H-pyrano[2'',3'':7,8]-isoflavone. Moreover, two known pterocarpans, erybraedin C and bitucarpin A, three known isoflavones, daidzein, 8-prenyldaidzein and bidwillon C, one known furocoumarin, pseudoisopsoralen and one known coumestan, coumestrol were isolated. The structures of the isolated compounds were established by means of 1D and 2D NMR spectroscopy, as well as mass spectrometry. Further cytotoxicity tests against cells related to the immune system (Jurkat T, Mono-Mac-6 and polymorphonuclear cells) showed a moderate activity of the known pterocarpan erybraedin C against all cell lines used (IC (50) values between 17.6-28.8 microM). In addition, erybraedin C was found to induce necrosis in leukaemia Jurkat T cells.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Phenolic constituents from Ephedra nebrodensis.

Two new phenolic glycosides, 4-hydroxy-3-(3-methyl-2-butenyl)phenyl beta-D-glucopyranoside (nebrodenside A) and O-coumaric acid beta-D-allopyranoside (nebrodenside B), were isolated from the aerial parts of Ephedra nebrodensis. In addition, O-coumaric acid glucoside, (-)-epicatechin, and (-)-ephedrine were also isolated. The structures were deduced from extensive 1D and 2DNMR spectroscopy (1H, 13C, DQF-COSY, TOCSY, GHSQC, GHMQC, ROESY) as well as mass spectrometry (EI and HR-MALDI). (-)-Epicatechin showed weak antiviral activity against Influenza A virus and very weak cytotoxicity against MDCK cells.

Catechin↗
PubMed2004

Structural investigation of pig metmyoglobin by 129Xe NMR spectroscopy.

The potentiality of xenon's sensitivity to its local magnetic environment is thoroughly investigated to probe internal structural differences between pig and horse metmyoglobin (MMb). These MMb's differ by 14 amino acids. One of these, Ile142 in horse MMb, is located in the proximal cavity, which is the xenon-binding site in horse MMb, and is replaced by Met142 in pig MMb. Specific and non-specific xenon-protein interactions are investigated here by 129Xe NMR chemical shifts and relaxation rate in aqueous solutions of pig MMb as a function of the xenon and protein concentrations. The results are complemented with 129Xe NMR data of the isostructural carbonmonoxy myoglobin (COMb), with computational calculations in order to highlight the structural differences between the cavities, and 1H NMR spectra to test the dependence of the 1H chemical shift on the addition of xenon. The 129Xe chemical shift NMR parameters are analysed quantitatively in terms of a two-site model. Xenon forms a 1:1 complex with the protein, characterized by an equilibrium binding constant K=[Xe]in/([Xe]out[MMb]), and exchanges rapidly between a cavity within the protein (X(ein)) and all other environments (Xe(out)). A comparison of equilibrium constant, K (74 M(-1)) in pig and K (146 M(-1)) in horse, reveals differences in affinity of xenon to the interior of pig MMb. Changes in xenon binding in both pig and horse MMb are also pointed out by other experimental results, e.g. the difference in the estimated delta(in), which is shifted downfield in pig MMb and upfield in horse MMb, with respect to 129Xe in buffer solution; the xenon-iron distance, 7.4 A, which is longer in the pig than was found in the horse, 5.3 A.

Animals↗
PubMed2002

Multinuclear NMR investigation of the NaDNA/ethidium bromide anisotropic system.

A combined use of (31)P, (23)Na, (2)H and (17)O NMR spectroscopies and polarized light microscopy has been employed to investigate the effect of the ethidium bromide (EB) binding on the liquid crystalline phase of concentrated double stranded DNA solutions. The optical textures and the (31)P and (23)Na NMR spectra of the DNA anisotropic solutions show that the intercalation of EB induces significant modifications either in the arrangements of the DNA rods and the surrounding ionic atmosphere. On the contrary, no indication of significant changes of the orientational order of the water molecules around DNA emerges from the water (2)H and (17)O NMR spectra.

Animals↗
PubMedDate not supplied

Solid-state 13C NMR study of poly(vinyl alcohol) gels.

Poly(vinyl alcohol) (PVA) with 55% and 61% syndiotacticity, and their related dry and hydrated gels obtained by two different freeze-thawing cycles have been investigated using the solid-state 13C CP-MAS NMR technique. From a comparative analysis of the spectra, evidence was obtained that the gelation process largely disrupts the intramolecular hydrogen-bonded network of the PVA. The addition of water to the dry gels favours their swelling, destroying intra-chain hydrogen bonds between hydroxyl groups as a function of the degree of tacticity and the gelation procedure, and promotes the formation of new networks of interchain hydrogen bonds. Information on the dynamics of the polymeric domains in the kilohertz range has been obtained from the analysis of the spin relaxation times T1rho(1H) and T1rho(13C) indicating that homogeneous arrangements of the amorphous or swollen polymeric chains exist, independent of the preparation method or the tacticity of the PVA chains.

Gels↗
PubMedDate not supplied

Topical anti-inflammatory activity of flavonoids and a new xanthone from Santolina insularis.

Bioactivity-guided fractionation of the methanol extract from the leaves of Santolina insularis led to the isolation of one new xanthone, (E)-3-(6-[(E)-3-hydroxy-3-oxo-1-propenyl]-9-oxo-9H-xanthen-2-yl)-2-propenoic acid, together with six known flavonoids: hispidulin, nepetin, cirsimaritin, rhamnocitrin, luteolin and luteolin 7-O-beta-D-glucopyranoside. The structures were elucidated by means of 1D-, 2D-NMR spectroscopy and mass spectrometry. The topical anti-inflammatory activity of all isolated compounds and extracts was investigated employing the croton oil-induced dermatitis in mouse ear. The most active compound, luteolin, showed an ID50 of 0.3 micromol/cm(2) and prevented ear oedema more effectively than an equimolar dose of indomethacin within 24 h.

Animals↗