Biomedical subjects

Judit Reményi

Publications and source records attributed to Judit Reményi.

6 recordsLinked to original sources

PubMed2006

The effect of the structure of branched polypeptide carrier on intracellular delivery of daunomycin.

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.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

A new class of semisynthetic anthracycline glycoside antibiotics incorporating a squaric acid moiety.

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).

Anthracyclines↗

PubMed2004

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

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.

Amino Acid Sequence↗

PubMed2003

Amplitude, phase, and hybrid ternary modulation modes of a twisted-nematic liquid-crystal display at approximately 400 nm.

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.

Journal Article↗

PubMed2003

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

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.

Antineoplastic Agents↗

PubMedDate not supplied

Drug targeting by macromolecules without recognition unit?

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.

Animals↗