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Synthetic Communications 01/2011; · 1.06 Impact Factor
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Krisztina Németh,
Gábor Tárkányi,
Erzsébet Varga, Tímea Imre,
Réka Mizsei,
Róbert Iványi,
Júlia Visy,
Julianna Szemán,
László Jicsinszky,
Lajos Szente,
Miklós Simonyi
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ABSTRACT: Capillary electrophoresis (CE) methods for chiral resolution of five antimalarial drugs (primaquine, tafenoquine, mefloquine, chloroquine and quinacrine) were developed by using a wide selection of neutral and anionic cyclodextrin (CD) derivatives. The use of sulfobutyl-β-CD and carboxymethyl-β-CD (CMBCD) resulted in good resolution of quinacrine and tafenoquine, respectively. New results are presented for resolutions of chloroquine and mefloquine. Application of carboxyalkyl- and sulfobutyl-CD derivatives provided improved resolution for primaquine. The impurity in primaquine sample detected by CE was identified as quinocide by MS and NMR. CMBCD provided not only the best separation of primaquine from quinocide but also the simultaneous complete resolution of both compounds.
Journal of pharmaceutical and biomedical analysis 09/2010; 54(3):475-81. · 2.45 Impact Factor
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ABSTRACT: N-glycan oligosaccharides of human serum alpha(1)-acid glycoprotein (AGP) samples isolated from 43 individuals (healthy individuals and patients with lymphoma and with ovarian tumor) were analyzed by MALDI-TOF mass spectrometry and a multivariate statistical method (linear discriminant analysis, LDA). 34 different glycan structures have been identified. From the glycosylation pattern determined by mass spectrometry fucosylation and branching indices have been calculated. These parameters show only small differences between the patient groups studied, but these differences are not sufficiently large to use as a potential biomarker. LDA analysis, on the other hand shows a very good separation between the three groups (with a classification of 88%). Cross-validation indicates that the method has predictive power: Identifying cancerous vs. healthy individuals shows 96% selectivity and 93% specificity; identification of lymphoma vs. the mixed group of healthy and ovarian tumor cases is also promising (72% selectivity and 84% specificity). The pilot study presented here demonstrates that mass spectrometry combined with linear discriminant analysis (LDA) may provide valuable data for identifying and studying the pathophysiology of malignant diseases.
Journal of Proteomics 08/2008; 71(2):186-97. · 4.88 Impact Factor
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ABSTRACT: A new anionic surfactant (RapiGest SF) was successfully used for site-specific analysis of glycosylation in human alpha-1-acid glycoprotein (AGP). By means of this analytical approach combined with capillary HPLC-mass spectrometry (and tandem mass spectrometry), the N-linked glycosylation pattern of AGP was explored. On the basis of mass matching and MS/MS experiments ca 80 different AGP-derived glycopeptides were identified. Glycosylation shows a markedly different pattern for the various glycosylation sites. At sites I and II, triantennary complex-type oligosaccharides predominate and at sites III, IV and V, tetra-antennary complex-type oligosaccharides predominate. Sites IV and V show the presence of additional N-acetyl lactosamine (Gal-GlcNAc) units (even higher degree of branching and/or longer antennae are also present).
Journal of Mass Spectrometry 12/2005; 40(11):1472-83. · 3.27 Impact Factor
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ABSTRACT: A new anionic surfactant (RapiGest SF) was successfully used for site-specific analysis of glycosylation in human alpha-1-acid glycoprotein (AGP). By means of this analytical approach combined with capillary HPLC-mass spectrometry (and tandem mass spectrometry), the N-linked glycosylation pattern of AGP was explored. On the basis of mass matching and MS/MS experiments ca 80 different AGP-derived glycopeptides were identified. Glycosylation shows a markedly different pattern for the various glycosylation sites. At sites I and II, triantennary complex-type oligosaccharides predominate and at sites III, IV and V, tetra-antennary complex-type oligosaccharides predominate. Sites IV and V show the presence of additional N-acetyl lactosamine (Gal-GlcNAc) units (even higher degree of branching and/or longer antennae are also present). Copyright © 2005 John Wiley & Sons, Ltd.
Biological Mass Spectrometry 10/2005; 40(11):1472 - 1483. · 3.41 Impact Factor
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ABSTRACT: The ultrahigh resolution and sensitivity of electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry have for the first time been exploited for the characterization of highly sialylated glycoproteins, using human alpha-1-acid glycoprotein as the model compound. An alternative approach to the widely used high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization (MALDI) assays is described. This new method does not require any enzymatic or chemical digestion (removal of sialyl groups or deglycosylation), chemical derivatization (introduction of chromophore groups), or preliminary chromatographic separation (HPLC or electrophoresis). Following ESI and accumulation of ions in a hexapole ion guide, ions are injected into the ICR cell. A selected mass window from the overall ion population is isolated and axialized prior to detection. After acquisition and Fourier transform of the transient signal the resulted spectrum is evaluated in order to determine the charge state of the detected ions and the isotope pattern of the measured protein glycoform. The presence of ions from the same glycoform with different charge states was confirmed. The advantages and limitations of the technique are discussed. Future prospects and possible applications are indicated.
Analytical Chemistry 10/2004; 76(17):4998-5005. · 5.86 Impact Factor
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ABSTRACT: Optimum conditions for the synthesis of aryl-dibenzo-oxaphosphorines (2) from the corresponding phosphonous chloride (1) were explored to avoid the formation of by-products (e.g., 4–6). The aryl-dibenzo-oxaphosphorines (2) were converted to the P-oxides (3), and were utilized in the synthesis of phosphinite-boranes 7 and Pt(II) complexes 8. Depending on the aryl substituent, the Pt(II) complex (8) was formed with cis and trans geometry. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:459–463, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20042
Heteroatom Chemistry 09/2004; 15(6):459 - 463. · 1.24 Impact Factor
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ABSTRACT: A series of new P-methylphenyl P-heterocycles are introduced. The para and ortho substituted 2,5-dihydro-1H-phosphole oxides (1a and 1b) were converted to the double-bond isomers (A and B) of 1,2-dihydrophosphinine oxides (3a and 3b) via the corresponding phosphabicyclo[3.1.0]hexane oxides (2a or 2b). Isomeric mixture (A and B) of the dihydrophosphinine oxides (3a and 3b) gave, in turn, the isomers (A and B) of phosphabicyclo[2.2.2]oct-5-enes (4a and 4b) or a phosphabicyclo[2.2.2]octa-5,7-diene (5) in Diels-Alder reaction with dienophiles. The bridged P-heterocycles (4 and 5) were useful in the photo- or thermoinduced fragmentation-related phosphinylation of hydroxy compounds and amines. The new precursors (4a and 4b) were applied in mechanistic investigations. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:443–451, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10176
Heteroatom Chemistry 06/2003; 14(5):443 - 451. · 1.24 Impact Factor
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ABSTRACT: 1-(2,4,6-Trialkylphenyl)phospholes 1a,b possess a moderate aromatic character. Despite of that they underwent a sigmatropic rearrangement at 150°C to afford 2H-phospholes 2a,b which by trapping with tolane, or in reaction with another unit of 2 gave [4 + 2] cycloadducts 3a,b, or in a reversible reaction, dimer 6, respectively. Dedimerization of species 6 at 150°C in the presence of tolane, or at 0°C under oxidative circumstances, led to 1-phosphanorbornadiene 3a, or phosphole oxide dimer 8, respectively. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:316–319, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10151
Heteroatom Chemistry 05/2003; 14(4):316 - 319. · 1.24 Impact Factor
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ABSTRACT: The binding property of parinaric acid, a polyunsaturated fatty acid, to bovine beta-lactoglobulin, has been studied by electrospray ionization mass spectrometry. Stable complexation was observed under acidic conditions in a molar ratio of 1:1. Competitive complexation experiments were performed using saturated and unsaturated fatty acid standards with different chain lengths and number of double bonds to study the specificity of the interaction. It can be concluded that formation of the parinaric acid-lactoglobulin complex is preferred even if the molar concentration of the other fatty acids is ten times higher. In cases of specific complex formation the protein must have an active site that is a good acceptor for the ligand molecule. Limited trypsinolysis was performed on the lactoglobulin molecule to identify which part is responsible for the complexation. An intermediate tryptic fragment with molecular mass of 5200 Da was found to have the same ability to bind parinaric acid as the intact protein. This disulfide-bonded residue, [41-70]S-S[149-162], might thus be involved in the specific complexation of parinaric acid to beta-lactoglobulin. This conclusion is consistent with previous information on this binding site.
Rapid Communications in Mass Spectrometry 02/2003; 17(22):2464-70. · 2.79 Impact Factor
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ABSTRACT: Binding of the polyunsaturated cis-parinaric acid to bovine beta-lactoglobulin (BLG) was studied by circular dichroism (CD), electronic absorption spectroscopy and mass spectrometry methods. Upon protein binding, the UV absorption band of parinaric acid is red shifted by ca. 5 nm, showing hypochromism and reduced vibrational fine structure, suggesting that the ligand binds as a monomer in non-planar geometry. In the CD spectra measured at pH 7.36 and 8.5 a strong, negative Cotton band appears centered at 310 nm (Delta epsilon = -25 M(-1) cm(-1)) corresponding to the long-wavelength absorption band of cis-parinaric acid. The source of this induced optical activity is the helical distortion of the polyene chromophore caused by the chiral protein environment. From CD spectral data the value of the association constant was calculated to be 4.7 x 10(5) M(-1) at pH 7.36. CD and mass spectrometry measurements showed that parinaric acid binds weakly to BLG in acidic solution, though small peaks at mass 18,559 and 18,645 can be obtained in the reconstructed electrospray mass spectrum; these correspond to the binding of parinaric acid in 1:1 stoichiometry to both monomer variants of BLG B and A. The hydrophobic interior cavity of BLG was assigned as the primary binding site of cis-parinaric acid.
FEBS Letters 07/2002; 520(1-3):81-7. · 3.54 Impact Factor
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ABSTRACT: The reaction of monoaza-15-crown-5 1 with bromoalkylphosphine oxides 2 and diphenylvinylphosphine oxide led to a new type of lariat ethers (3a–d), one member of which (3a) was deoxygenated to the corresponding phosphine (4). The substituent at the nitrogen atom had a great impact on the extraction ability of the azacrown. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10:573–576, 1999
Heteroatom Chemistry 11/1999; 10(7):573 - 576. · 1.24 Impact Factor
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Tetrahedron Letters 46(10):1655-1658. · 2.68 Impact Factor
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György Keglevich,
Nóra Balázsdi Szabó,
Namkhainyambuu Bat Amgalan,
Renáta Farkas,
Henrietta Forintos,
László Hegedűs, Tímea Imre,
János Kovács,
Tamás Körtvélyesi,
Krisztina Ludányi,
Tibor Novák,
Irina Leonovna Odinets,
Ágnes Polonkáné Bálint,
Melinda Sipos,
Jankowski Stefan,
Helga Szelke,
Áron Szöllősy,
Károly Vékey,
Natalya Mikchailovna Vinogradova
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ABSTRACT: A kutatás három fő szálon futott, egyrészt az 5- és 6-tagú, másrészt a 7- és 8-tagú - ez utóbbi esetben áthidalt - P-heterociklusok területén, harmadrészt egy inverz Wittig-típusú reakció témájában. Újfajta foszfol- és a 3-as helyzetben foszforfunkciót tartalmazó 1,2,3,6-tetra- és 1,2,3,4,5,6-hexahidrofoszfinin P-ligandokat (ill. ez utóbbiak prekurzorait) tettük hozzáférhetővé, amelyeket átmeneti fémkomplexekké is átalakítottunk. A P-ligandok és a komplexek térszerkezetét felderítettük és ez utóbbiak egy részét katalizátorként is kipróbáltuk. Jónéhány dibenzooxafoszforint - közöttük optikai aktivitással rendelkező származékokat is - előállítottunk. A ligandok platina-komplexeit is elkészítettük. A kutatás másik vonalán új 7-foszfanorbornén, ill. 2-foszfabiciklo[2.2.2]oktén 2-oxid származékokat vezettünk be, egyrészt új szubsztituensek, másrészt új dienofilek alkalmazásával. A prekurzorokat reakcióképes intermedierek képzésén át foszforilezési reakciókban hasznosítottuk. Tanulmányoztuk a reakciók mechanizmusát és oxafoszfabiciklookténeket is vizsgáltunk. A harmadik témában a P-aril gyűrűs foszfin-oxidok és a dialkilacetiléndikarboxilát béta-oxofoszforánokat eredményező reakcióinak mechanizmusát derítettük fel és megfontoltuk az oxafoszfetének mint intermedierek lehetőségét. A béta-oxofoszforánokat kerülő szintézissel is hozzáférhetővé tettük és tanulmányoztuk néhány jellemző reakciójukat. | The research was performed in three topics, on one hand in the topic of 5- and 6-membered P-heterocycles, on the other hand in the field of 7- and 8-membered P-cycles including bridged derivatives, and finally in the topic of the inverse Wittig type reaction. New phosphole and 1,2,3,6-tetra- and 1,2,3,4,5,6-hexahydrophosphinine P-ligands - these latter with exocyclic P-function in position three - were made available that were also transformed to transition metal complexes. Stereostructure of the P-ligands and complexes was evaluated and a part of the latter was tested as catalyst. A number of dibenzooxaphosphorines and their platinum complexes were also prepared. In the second line of the research, new 7-phosphanorbornene- and 2-phosphabicyclo[2.2.2]octene 2-oxide derivatives were introduced and utilized in fragmentation related phosphorylation of nucleophiles. Beside the mechanistic studies, oxaphosphabicyclooctenes were also studied. In the third topic, the mechanism of the inverse Wittig type reaction of cyclic phosphine oxides and dialkyl acetylenedicarboxylate resulting in beta-oxophosphoranes was studied. Oxaphosphetes were considered as possible intermediates. The beta-oxophosphoranes were also prepared by an independent synthesis and some of their reactions were investigated.
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ABSTRACT: Kutatásaink során peptidek, proteinek, polilizinek és molekuláris komplexek tömegspektrometriás vizsgálatával foglalkoztunk. Molekuláris komplexek körében mind szolvatált fémionokkal, mind pedig antitest-antigén komplexekkel foglalkoztunk, ezeket sikeresen előállítottunk és tömegspektrometriával jellemeztünk. Legfontosabb eredményünk egy olyan új peptidfragmentációs modell kidolgozása, mely peptidek tömegspektrumának, tandem tömegspektrumának elméleti meghatározását teszi lehetővé. A modell alapján egy olyan új szoftvert fejlesztettünk ki, mely a világon egyedülálló, prediktív jellegű és a gyakorlatban jól használható. A modell "szemi-empirikus" megoldás: az elméleti, általunk kifejlesztett MassKinetics algoritmus alapján működik, a fragmentáció leírásához szükséges fizikai, fiziko-kémiai paramétereket viszont empirikusan meghatározott paraméterekkel helyettesíti. A program a proteomika eszköztárát jelentősen továbbfejleszti, szabadalmaztatást követően világszerte elérhetővé tesszük. | We have studied peptides, proteins, polylysins and various molecular complexes by mass spectrometry. In the latter class we have produced and characterized both solvated metal ions and antibody-antigen complexes. Our most important result is development of a new peptide fragmentation model which allows theroretical prediction of tandem mass spectra. Based on this model a new software has been developed which is unique, has predictive value and can be used easily. It is a "semi-empirical" method, as it is based on the theoretical MassKinetics algorithm, but the physical and physico-chemical parameters needed to describe peptide fragmentation are determined by an empirical approach. The program can be advantageously used in the proteomics field and will be made widely available after patenting.
