Judit Reményi

Publications (13)27.59 Total impact

• Article: Synthesis and in vitro antitumor effect of vinblastine derivative-oligoarginine conjugates.

  Zoltán Bánóczi, Álmos Gorka-Kereskényi, Judit Reményi, Erika Orbán, László Hazai, Natália Tökési, Judit Oláh, Judit Ovádi, Zoltán Béni, Viktor Háda, Csaba Szántay, Ferenc Hudecz, György Kalaus
  [show abstract] [hide abstract]
  ABSTRACT: Vinblastine is a widely used anticancer drug with undesired side effects. Its conjugation with carrier molecules could be an efficient strategy to reduce these side effects. Besides this, the conjugate could exhibit increased efficiency against resistant cells, e.g., due to the altered internalization pathway. Oligoarginines, as cell-penetrating peptides, can transport covalently attached compounds into different kinds of cells and enhance the efficiency of those compounds. We report here the coupling of vinblastine through its carboxyl group at position 16 with the N-terminal amino function of L-Trp methyl ester. After hydrolysis of the ester group, 17-desacetylvinblastineTrp was conjugated to the N-terminal amino group of oligoarginine via the C-terminal carboxyl group of the Trp moiety in solution. The antitumor effect of conjugates was studied on sensitive and resistant human leukemia (HL-60) cells in vitro. Our data suggest that all conjugates investigated possess an antiproliferative effect against the studied cells. However, the effect was dependent on the number of Arg residues in the conjugates: Arg₈ > Arg₆ ≫ Arg₄. The conjugate with Arg₈ exhibited similar efficicacy as compared with free 17-desacetylvinblastineTrp. The in vitro studies also showed that the tubulin binding ability of vinblastine was essentially preserved even in the octaarginine conjugate. We also observed that two isomers were formed during conjugation. These isomers showed different levels of activity against tubulin polymerization in vitro and in vivo. The 17-desacetylvinblastineTrp-Arg₈-1 isomer conjugate possessed high selectivity against the mitotic spindles. HRMS and NMR data suggest that 17-desacetylvinblastineTrp-Arg₈-1 and 17-desacetylvinblastineTrp-Arg₈-2 are epimers at the tryptophan α carbon atom.
  Bioconjugate Chemistry 10/2010; 21(11):1948-55. · 4.93 Impact Factor
• Article: Hybrid multinary modulation using a phase modulating spatial light modulator and a low-pass spatial filter.

  Zoltán Göröcs, Gábor Erdei, Tamás Sarkadi, Ferenc Ujhelyi, Judit Reményi, Pál Koppa, Emoke Lorincz
  [show abstract] [hide abstract]
  ABSTRACT: We propose a method for performing binary intensity and continuous phase modulation of beams with a spatial light modulator (SLM) and a low-pass spatial filtering 4-f system. With our method it is possible to avoid the use of phase masks in holographic data storage systems or to enhance the phase encoding of the SLM by making it capable of binary amplitude modulation. The data storage capabilities and the limitations of the method are studied.
  Optics Letters 09/2007; 32(16):2336-8. · 3.40 Impact Factor
• Article: New ferrocene containing peptide conjugates: synthesis and effect on human leukemia (HL-60) cells.

  Zsanett Miklán, Rita Szabó, Virág Zsoldos-Mády, Judit Reményi, Zoltán Bánóczi, Ferenc Hudecz
  [show abstract] [hide abstract]
  ABSTRACT: Data reported in this article describe the synthesis of Arg-rich oligopeptide conjugates of ferrocenecarboxylic acid on solid support with two different strategies and for the first time, the successful preparation of peptide conjugates of ferrocenylacrylic acid in solution. The antitumor effect of conjugates was analyzed by MTT assay in vitro. We demonstrated that ferrocenylacrylic acid possessing an enone (--CH==CH--CO--) moiety exhibited remarkable antiproliferative effect against human leukemia cells (HL-60) in vitro, but its effect was not improved by conjugation with hexa- or octaarginines. However, we observed highly increased water-solubility. In contrast, the results provide evidence that conjugation of ferrocenecarboxylic acid to Arg(n) (n = 6, 8) improved not only its water-solubility, but also antitumor effect on human leukemia cells in vitro.
  Biopolymers 02/2007; 88(2):108-14. · 2.87 Impact Factor
• Article: The effect of the structure of branched polypeptide carrier on intracellular delivery of daunomycin.

  Judit Reményi, Gabriella Csík, Péter Kovács, Francesca Reig, Ferenc Hudecz
  [show abstract] [hide abstract]
  ABSTRACT: The conjugate of acid labile cis-aconityl-daunomycin (cAD) with branched chain polypeptide, poly[Lys(Glui-DL-Alam)] (EAK) was very effective against L1210 leukemia in mice. However, Dau attached to a polycationic polypeptide, poly[Lys(Seri-DL-Alam)] (SAK) exhibited no in vivo antitumor effect. In order to understand this difference we have performed comparative in vitro studies to dissect properties related to interaction with the whole body (e.g., biodistribution) from those present at cellular or even molecular level. We report here (a) the kinetics of acid-induced Dau liberation, (b) interaction with DPPC phospholipid bilayer, (c) in vitro cytotoxic effect on different tumor cells, and (d) intracellular distribution in HL-60 cells of polycationic (cAD-SAK) and amphoteic (cAD-EAK) conjugates. Fluorescence properties of the two conjugates are also reported. Our findings demonstrate that the kinetics of the drug release, intracellular distribution and in vitro cytotoxic effect are rather similar, while the effect on DPPC phospholipid bilayer and fluorescence properties of the two conjugates are not the same. We also found that the in vitro cytotoxicity is cell line dependent. These observations suggest that the structure of the polypeptide carrier could have marked influence on drug uptake related events.
  Biochimica et Biophysica Acta 04/2006; 1758(3):280-9. · 4.66 Impact Factor
• Article: A new class of semisynthetic anthracycline glycoside antibiotics incorporating a squaric acid moiety.

  Ferenc Sztaricskai, Anita Sum, Erzsébet Roth, István F Pelyvás, Szabolcs Sándor, Gyula Batta, Pál Herczegh, Judit Reményi, Zsanett Miklán, Ferenc Hudecz
  [show abstract] [hide abstract]
  ABSTRACT: Treatment of the squaric acid amide esters (7, 9) of anthracycline glycoside antibiotics with aliphatic and aromatic primary and secondary amines, amino acids, peptides and aminodeoxy sugars furnished the new asymmetric diamides 16-19, 25-30, 32, 34 and 38-40 in stereoselective reactions which do not require protecting group-manipulations. The IC50 = 0.12 microM value measured for daunorubicin (1) on human leukemia (HL-60) cells is comparable to those obtained for the daunomycin-L-leucyl squaric acid diamide (30, IC50 = 0.18 microM) and the corresponding D-galactosamine derivative (40, IC50=0.22 microM).
  The Journal of Antibiotics 12/2005; 58(11):704-14. · 1.65 Impact Factor
• Source

  Available from: Zsuzsa Majer

  Article: Synthesis, conformation, and immunoreactivity of new carrier molecules based on repeated tuftsin-like sequence.

  Gábor Mezö, Adrián Kalászi, Judit Reményi, Zsuzsa Majer, Agnes Hilbert, Orsolya Láng, László Köhidai, Krisztina Barna, Dezsö Gaál, Ferenc Hudecz
  [show abstract] [hide abstract]
  ABSTRACT: Sequential oligopeptides based on a pentapeptide (TKPKG) derived from tuftsin with different lengths were synthesized by stepwise solid phase methodology. These highly soluble oligomers were nontoxic on mouse spleen cells, and other biological data suggested that tuftsin-like properties were also presented. The (TKPKG)n (n=2,4,6,8) oligopeptides were not immunogenic; however, they increased sheep red blood cells (SRBC) antigen specific antibody response in mice, demonstrating their immunostimulatory effect. Chemotactic activity was also found on J774 monocyte cells, while MRC5 fibroblasts were chemotactically nonresponders to the tested forms of tuftsin. These oligomers showed unordered and flexible structure by CD measurements, confirmed by computer modeling studies indicating also a fairly good accessibility of the epsilon-amino group of each lysine residue. Data suggest that these new oligotuftsin derivatives can be considered as promising carriers for synthetic vaccine.
  Biopolymers 05/2004; 73(6):645-56. · 2.87 Impact Factor
• Article: Amplitude, phase, and hybrid ternary modulation modes of a twisted-nematic liquid-crystal display at approximately 400 nm.

  Judit Reményi, Péter Várhegyi, László Domján, Pál Koppa, Emõke Lõrincz
  [show abstract] [hide abstract]
  ABSTRACT: Applicability of a commercial twisted-nematic liquid-crystal display is examined at approximately 400 nm. Different modulation modes predicted by Jones-matrix calculus are experimentally tested. High contrast amplitude modulation with negligible loss, high contrast and low loss hybrid ternary modulation, and 1.5pi continuous phase delay without intensity modulation and with low loss are presented. Simulation results of a 4f holographic system prove the usefulness of the high contrast for amplitude modulation, and the importance of pi phase difference between high transmission white levels in a hybrid ternary modulation.
  Applied Optics 07/2003; 42(17):3428-34. · 1.41 Impact Factor
• Source

  Available from: elte.hu

  Article: Isomer-dependent daunomycin release and in vitro antitumour effect of cis-aconityl-daunomycin.

  Judit Reményi, Barbara Balázs, Sára Tóth, András Falus, Gábor Tóth, Ferenc Hudecz
  [show abstract] [hide abstract]
  ABSTRACT: Two isomers of cis-aconytil-daunomycin (cAD) were isolated after the reaction of daunomycin with cis-aconitic-anhydride. The structure of the isomers was identified by MS-spectroscopy and 1H and 13C NMR experiments. In contrast with the assumptions described earlier, our results show that the two isomers belong to the cis- and trans-isomers of the alpha-monoamide of cis-aconityl-daunomycin, respectively. We found that the pH dependent daunomycin release is different for the two isomers. Comparative analysis of the in vitro antitumour effect of the isomers on c26 colon carcinoma and on MDA-MB 435P human breast carcinoma cell lines showed that cAD-1 is more potent than cAD-2, but the extent of differences is tumour cell dependent. The results of this study might be appreciated in the light of the use of acid-labile spacer for the design and preparation of protein/peptide conjugates of drugs by indicating that isomers could possess markedly different biological activity.
  Biochemical and Biophysical Research Communications 05/2003; 303(2):556-61. · 2.48 Impact Factor
• Article: Drug targeting by macromolecules without recognition unit?

  Ferenc Hudecz, Judit Reményi, Rita Szabó, György Kóczán, Gábor Mezo, Péter Kovács, Dezso Gaál
  [show abstract] [hide abstract]
  ABSTRACT: his review will summarize available information on the ability of macromolecular conjugates containing no specific recognition motifs to deliver anthracyclines (daunomycin, adriamycin) or methotrexate to target cells such as tumour cells or macrophages. Conjugates with natural (proteins, DNA, carbohydrates) and synthetic macromolecules (linear and branched chain poly-alpha-amino acids, non-biodegradable DIVEMA, HPMA etc.) will be reviewed. Experimental data from several laboratories indicate that these conjugates are taken up by cells mainly by fluid-phase or adsorptive endocytosis. It is believed that these processes do not involve 'specific receptors'. Two examples of methotrexate and daunomycin conjugates will be discussed to show the effect of the chemical structure of branched chain polypeptides on the uptake and antitumour or antiparasitic (Leishmania donovani infection) efficacy of conjugates.
  Journal of Molecular Recognition 16(5):288-98. · 3.31 Impact Factor
• Article: Ternary phase-amplitude modulation with twisted nematic liquid crystal displays for Fourier-plane light homogenization in holographic data storage

  László Domján, Pál Koppa, Gábor Szarvas, Judit Reményi
  [show abstract] [hide abstract]
  ABSTRACT: Holographic data storage applications often use liquid crystal displays as spatial light-amplitude modulators for writing data images. The hologram created in the Fourier plane is usually applied to store the information, since this plane supplies optimal data density. A well known technique for homogenizing the light distribution in the Fourier plane is the application of external random phase modulating masks. The requirement for pixel by pixel matched positioning of the phase modulating mask and the pixels of the spatial light-amplitude modulator is hard to solve in the optical systems and any positioning error leads to significant signal degradations. The article analyses the possibilities of realizing the required simultaneous amplitude and phase modulation of light with the application of a single LCD. Twisted nematic LCDs with different maximal birefringence are numerically investigated using the Jones matrix method. Elliptical incident and exit polarizations are proposed, by which ternary phase-amplitude modulation (+1,–1,0) can be realized. Test measurements are also presented that demonstrate the validity of the calculated results.
  Optik - International Journal for Light and Electron Optics.
• Article: Epitópok illetve antimikrobiális hatású peptidek, peptidszármazékok célzott bevitele makrofág típusú sejtekbe = Targeting of epitope or antimicrobial peptides and derivatives to macrophages

  Ferenc Hudecz, Szilvia Erika Bősze, György Kóczán, László Kőhidai, Gábor Mezo, Rita Oláhné Szabó, Éva Rajnavölgyi, Judit Reményi, Regina Tugyi
  [show abstract] [hide abstract]
  ABSTRACT: A kutatás során számos olyan új vegyület készült el, amelyek segítségével tisztázni lehet epitóp peptidek és hatóanyagok célsejtbe (makrofágba) juttatásának szerkezeti illetve funkcionális feltételeit. Vizsgálataink fontos eredménye olyan biokonjugátumok előállítása volt, amelyekben az alkotórészek a kémiai kötés kialakítása után is megtartották biológiai funkciójukat (pl. T-sejt válasz indukció, ellenanyagfelismerés, antituberkulotikus hatás). A nagyrészt nívós nemzetközi folyóiratokban közölt eredmények közül kiemelkedik annak a jelenségnek a leírása és sokoldalú bizonyítása, amely szerint a makrofágok polianionos szintetikus makromolekulák felvételére scavenger A receptort ?használnak?. Kimutattuk, hogy efféle molekulához kovalensen kapcsolt riporter egység (fluorofor) bekerül a sejtbe. Ez a megfigyelés, valamint a kemotaxis alapú célbajuttatás jelenségének leírása lényegesek lehetnek makromolekulára alapozott célbajuttató rendszerek kifejlesztésében (makromolekula kiválasztás, intracelluláris kötés stabilitás stb.) és segíthetik új gyógyszerek kifejlesztését. | We have prepared a number of new bioconjugates and their components. These compounds proved to be useful for understanding and identification of structural and functional requirements for targeting macrophages. The components of new conjugates prepared preserved their funcional properties (e.g. T cell response provoking capacity, antibody recognition, antituberculotic activity). Among the most important findings we describe that macrophages could internalize polyanionic, synthetic compounds as well as their conjugates. We found that for this purpose scavenger A receptors are utilised. As another important result of the last few years we also proposed and provided experimental evidence concerning the principle of chemotaxis based drug/epitop delivery. Results achieved were presented in International journals and conferences. Our findings could be considered as useful contribution to the development of macromolecule based targeting for drug research and/or immundiagnostics.
• Article: Hatékony tumorellenes készítmények előállítása target és drug molekulák kombinációjával = Synthesis of effective antitumoricidal compounds with the combination of target and drug molecules

  Gábor Mező, Orsolya Csuka, Dezső Gaál, Annamária Jakab, Magdolna Kovács, Orsolya Láng, Judit Reményi, Gitta Zsófia Schlosser, Borbála Vincze
  [show abstract] [hide abstract]
  ABSTRACT: Az irányított tumorterápiában alkalmazható új vegyületeket terveztünk és állítottunk elő. GnRH-III dimer származékok nagyobb tumorellenes hatást és kisebb endokrin aktivitást mutattak, mint a monomer. Enzim stabilitásuk szintén fokozódott. In vivo tumorellenes hatásukat HT-29 vastagbél tumort hordozó egereken tesztelve 50%-os gátlást értünk el. GnRH-I illetve GnRH-II és GnRH-III hormone peptideket tartalmazó vegyes dimereket is előállítottunk. T47-D emlőtumor sejteken 80% fölötti gátlást tapasztaltunk egy GnRH-I és GnRH-III peptidet tartalmazó dimer esetén. A dimerek szabadalmaztatása folyamatban van. A GnRH-III hormont hatóanyagok szállítására is felhasználtuk. Antraciklineket kapcsoltunk hozzá észter-, hidrazon- oxim és amidkötéssel. Az utobbi kivételével valamennyi konjugátum jelentős in vitro tumorellenes hatást mutatott. A daunorubicin-GnRH-III oximkötésű konjugátumot választottuk ki in vivo kísérletekhez C26 egér vastagbéltumort hordozó egereken. Ha a kezelést a 4. és 7. napon végeztük a tumorbeültetést követően, 40-50%-os tumornövekedés gátlást kaptunk (15 mg/kg Dau hatóanyag tartalom mellett). Ugyanakkor a konjugátum kivédte a drog toxikus hatását, és túlélésnövekedést is eredményezett a szabad droghoz képest. Ez az első olyan eredmény, ahol oximkötéssel konjugált daunorubicin származékkal tumorellenes hatást értek el. Tuftsin-szerű hordozómolekulák alkalmazásával kemotaxison alapuló hatóanyag célbajuttatást tudtunk megvalósítani. | New derivatives for targeted cancer therapy were developed. Dimers derived from GnRH-III had higher antitumor effect on cancer cells and lower activity on LH secretion than the monomer. Enhanced enzymatic stability of the dimers was also determined. The in vivo antitumor effect of the dimers was studied on HT-29 colon tumor bearing mice and 50% tumor growth inhibition was detected. Asymmetric dimer derivatives derived from GnRH-I or GnRH-II and GnRH-III were prepared. The combination of GnRH-I and GnRH-III resulted in a superagonist compound having 80% in vitro antiproliferative effect on T47-D human breast cancer cells. GnRH-III was also used as targeting moiety for anticancer drug delivery. Anthracyclines were attached to it via ester, hydrazone, oxime or amide bond. Except amide bond containing derivatives all compounds with other type of linkage have significant antitumor activity. Oxime bond-linked Daunorubicin?GnRH-III conjugate was selected for in vivo studies on C26 murine colon carcinoma bearing mice. The results showed that the application of the conjugate prevent the toxic side effect of the free drug. The highest tumor growth inhibition (40-50%) was observed when the treatments were performed on days 4 and 7 after tumor transplantation using 15 mg Dau content in conjugate/kg body weight. This is the first study indicating significant antitumor effect of a Dau-conjugate with oxime linkage. Chemotactic drug targeting with tuftsin like carriers was also used.
• Article: Potenciálisan biológiailag aktív fémorganikus vegyületek - ferrocészubsztituált heterociklusok - és peptid-konjugátumaik szintézise, szerkezet-felderítése és komplex nagyműszeres (NMR, IR, UP, Mössbauer spektroszkópiai és Röntgen-diffrakciós) vizsgálata = Synthesis, structure determination and complex instrumental (NMR, IR, UP, Mössbauer spectroscopic and x-ray diffraction) study on organometallic compounds - ferrocenyl-substituted heterocycles - and their peptide derivatives with expected biolo

  Pál Sohár, Zoltán Bánóczi, Antal Csámpai, Balázs Fábián, Ferenc Hudecz, György Kóczán, Krisztina Kovács, Veronika Kudar, Árpád Kuik, Gábor Magyarfalvi, Judit Reményi, Árvácska Ilona Sárpátki, Rita Skodáné dr. Földes, Zsolt Szarka, György Tarczay, György István Túrós, Virág Zsoldosné dr. Mády
  [show abstract] [hide abstract]
  ABSTRACT: Tanulmányoztuk a ferrocén-szubsztiutució hatását heterociklusok képződésére. Hatástani vizsgálatokhoz változatos szerkezetű fc-származékok előállítására törekedtünk. Előállítottunk (het)aril-fc kalkonokat, s pirazol/in-származékaikat. Etilazido-fc-akrilátból foszforilideken át többféle hetaril-vegyületet nyertünk. Piridazinonil-fc-t és bisz-analógját előállítva, fázistranszfer diallilezést követő metatézissel ferrocenofánokhoz jutottunk. Hidrazinnal két fc-hidas makrociklusokat nyertünk, tanulmányoztuk konformációjukat, s elkészítettük Pd-komplexeiket. Acilferrocének tio/metiltio-szemikarbazonjaiból DMAD-val változatos heterociklusokat kaptunk. Vizsgáltuk diacil-fc-hidrazonok cikloaddícióit. A reaktivitásbeli eltéréseket és NMR-úton igazolt molekuladinamikát számításokkal értelmeztük. Az új vegyületek szerkezetét spektroszkópiával (IR, NMR, MS) és röntgendiffrakcióval tisztáztuk. Az új fc-származék in vitro tumorgátló hatását vizsgáltuk humán leukémia sejteken, a leghatékonyabb vegyületek hatását rezisztens sejteken is és hasonlóan jó növekedésgátlást észleltünk. Oligoarginin komponensekkel előállítottuk a fc-karbonsav és a fc-akrilsav új peptid-konjugátumait és meghatároztuk a sejtnövekedés-gátló hatást HL-60 sejtvonalon. Előállítottunk fc-(glioxil)-aminosav- és -szteroid-kalkon-konjugátumokat Pd-katalizált karbonilezéssel. Módszert dolgoztunk ki heterodiszubsztituált ferrocének 1,1'-dijód-ferrocénből kiinduló homogén katalitikus szintézisére. | The effect of ferrocene (fc) substituent on the formation of heterocycles was studied. For screening we produced a variety of fc compounds. We prepared (het)aryl-fc chalcones and their pyrazol/(in)e derivatives. From ethyl-azido-fc-acrylate some aryl-heterocycles were obtained. We prepared pyridazinonyl-fc and its bis analogue, from which via phase transfer diallylation and metathesis we obtained different ferrocenophanes. The reactions with hydrazine gave macrocycles with two fc bridges. The molecular dynamics was studied and Pd-complexes were prepared. The reactions of DMAD with tio/methylthiosemicarbazones of acyl-fc's yielded new heterorings. We studied the hydrazones and their cycloadditions. The structure-reactivity relationships and the molecular dynamics revealed by NMR were interpreted by calculations. The structures of the novel compounds were cleared by spectroscopy (IR,NMR, MS) and x-ray analysis. The in vitro antitumor activity of novel fc-derivatives were investigated on human leukemia cells. The most effective ones were also studied on resistant cells and gave good results. Using oligoarginin components, peptide conjugates of fc-carboxylic and -acrylic acid were obtained, and their antiproliferative effect was determined on HL-60 cells. Fc-(glyoxyl) amino acid- and steroid-chalcone-conjugates were synthesised by Pd-catalysed carbonylation. We elaborated a homogeneous catalytic route towards heterodisubstituted fc's from 1,1'-diiodo-fc.