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Dive into the research topics where Tamara Pajpanova is active.

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Featured researches published by Tamara Pajpanova.


Archives of Microbiology | 2003

Molecular cloning, expression and characterization of three distinctive genes encoding methionine aminopeptidases in cyanobacterium Synechocystis sp. strain PCC6803

Anelia Atanassova; Mamoru Sugita; Masahiro Sugiura; Tamara Pajpanova; Ivan Ivanov

Methionine aminopeptidase, known to be encoded by single genes in prokaryotes, is a cobalt-dependent enzyme that catalyzes the removal of N-terminal methionine residues from nascent polypeptides. Three ORFs encoding putative methionine aminopeptidases from the genome of cyanobacterium Synechocystis sp. strain PCC6803, designated as slr0786 (map-1), slr0918 (map-2) and sll0555 (map-3) were cloned and expressed in Escherichia coli. The purified recombinant proteins encoded by map-1 and map-3 had much higher methionine aminopeptidase activity than the recombinant protein encoded by map-2. Comparative analysis revealed that the three recombinant enzymes differed in their substrate specificity, divalent ion requirement, pH, and temperature optima. The broad activities of the iso-enzymes are discussed in light of the structural similarities with other peptidase families and their levels of specificity in the cell. Potential application of cyanobacterial MetAPs in the production of recombinant proteins used in medicine is proposed. This is the first report of a prokaryote harboring multiple methionine aminopeptidases.


Amino Acids | 1997

Canavanine derivatives useful in peptide synthesis

Tamara Pajpanova; S. Stoev; Evgeny Golovinsky; G. J. Krauß; J. Miersch

SummaryThe objective of this work is to investigate the possibilities for introducing the currently used Nα-, NG- and C-protective groups into the canavanine molecule and the preparation of canavanines selectively blocked at the guanidino function. These novel compounds will find application in the synthesis of canavanine derivatives expected to be amino acid antimetabolites and of canavanine modified biologically active peptides.


Amino Acids | 2012

Comparative study of the interaction of synthetic methionine-enkephalin and its amidated derivate with monolayers of zwitterionic and negatively charged phospholipids

A. Tsanova; A. Jordanova; G. As. Georgiev; Tamara Pajpanova; Evgeny Golovinsky; Zdravko Lalchev

Using Langmuir’s monolayer technique, the surface behavior and the interaction of the synthetic neuropeptide methionine-enkephalin (Met-enk) and its amidated derivate (Met-enk-NH2) with monolayers of the zwitterionic dimyristoylphosphatidylcholine (DMPC) and the negatively charged dimyristoylphosphatidylglycerol (DMPG) were studied. The surface tension (γ, mN/m) of DMPG and DMPC monolayers as a function of time (after injection of the peptide under the interface) was detected. The decrease in γ values showed that there was a strong penetration effect of both types of Met-enk molecules into the monolayers, being significantly stronger for the amidated derivate, Met-enk-NH2. We suggest that the interaction between the neuropeptides and DMPC was predominantly determined by peptides amphiphilicity, while the electrostatic forces play significant role for the insertion of the cationic Met-enk-NH2 in DMPG monolayers, especially at high packing densities. Our results demonstrate the potential of lipid monolayers formed in Langmuir’s trough to be successfully used as an elegant and simple membrane models to study lipid–peptide interactions at the air/water interface.


Amino Acids | 2014

Interaction of methionine-enkephalins with raft-forming lipids: monolayers and BAM experiments.

A. Tsanova; A. Jordanova; T. Dzimbova; Tamara Pajpanova; Evgeny Golovinsky; Zdravko Lalchev

Enkephalins (Tyr-Gly-Gly-Phe-Met/Leu) are opioid peptides with proven antinociceptive action in organism. They interact with opioid receptors belonging to G-protein coupled receptor superfamily. It is known that these receptors are located preferably in membrane rafts composed mainly of sphingomyelin (Sm), cholesterol (Cho), and phosphatidylcholine. In the present work, using Langmuir’s monolayer technique in combination with Wilhelmy’s method for measuring the surface pressure, the interaction of synthetic methionine–enkephalin and its amidated derivative with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), Sm, and Cho, as well as with their double and triple mixtures, was studied. From the pressure/area isotherms measured, the compressional moduli of the lipids and lipid–peptide monolayers were determined. Our results showed that the addition of the synthetic enkephalins to the monolayers studied led to change in the lipid monolayers characteristics, which was more evident in enkephalinamide case. In addition, using Brewster angle microscopy (BAM), the surface morphology of the lipid monolayers, before and after the injection of both enkephalins, was determined. The BAM images showed an increase in surface density of the mixed surface lipids/enkephalins films, especially with double and triple component lipid mixtures. This effect was more pronounced for the enkephalinamide as well. These observations showed that there was an interaction between the peptides and the raft-forming lipids, which was stronger for the amidated peptide, suggesting a difference in folding of both enkephalins. Our research demonstrates the potential of lipid monolayers for elegant and simple membrane models to study lipid–peptide interactions at the plane of biomembranes.


Amino Acids | 2000

Synthesis and biological activity of canavanine hydrazide derivatives

J. Miersch; Konstantin Grancharov; Tamara Pajpanova; Svoboda Tabakova; S. Stoev; Krauss Gj; Evgeny Golovinsky

Summary. The canavanine derivatives L-canavanine hydrazide (CH), L-canavanine-bis-(2-chloroethyl)hydrazide (CBCH) and L-canavanine phenylhydrazide (CPH) were synthesized and evaluated for biological activity in microorganisms, plants and tumor cells using canavanine as a positive control. (1) In microbial systems, the compounds exerted activity, as assessed in 14 bacterial strains. The effect of canavanine was easily removed by equimolar concentrations of arginine or ornithine, while the effect of CBCH or CPH was abolished by 10-fold excess of arginine or 10- to 100-fold excess of ornithine. (2) In plants, the activity of CH and CBCH were relatively low, whereas the inhibitory potential of CPH was comparable or even superior to that of canavanine, resulting at 1 mM concentration in a nearly complete block of tomato cell growth, and reducing by up to 80% the length of radicles of cress, amaranth, cabbage and pumpkin. (3) In pumpkin seeds, CPH or canavanine induced the synthesis of four small heat shock proteins of hsp-17 family in the pH range of 6 to 7.5. The proteins exhibited in both cases a similar profile, but differed in the timing of their expression and/or accumulation. With canavanine, the highest hsp-17 expression was found after 48 h of drug treatment, while with CPH this maximum was shifted to 24 h. (4) CPH proved to be highly cytotoxic against Friend leukemia cells in culture, exceeding by one order of magnitude the cytotoxicity of canavanine. The effect of canavanine was completely removed in the presence of equimolar amounts of arginine, while a 20-fold excess of arginine failed to abolish the cytotoxicity of CPH. Thus, a proper hydrazide modification of canavanine may lead to a significant increase in its growth-inhibitory activity and to a change in the mode of action of the parent compound.


Amino Acids | 2000

Synthesis and antibacterial activity of some new non-proteinogenic amino acids containing thiazole residues

M. Stanchev; Tamara Pajpanova; Evgeny Golovinsky

Summary. Some new thioamides and thiazoles have been synthesized using canavanine, S-cysteine, homo-S-cysteinesulfonamides and their N-ω-aminoethylated derivatives as adducts in order to investigate the structure-antimicrobial activity relationships. The compounds showed substantial antibacterial activity in vitro against various gram-positive (Staphylococcus aureus, Bacillus cereus etc.) and gram-negative (Escherichia coli, Proteus vulgaris etc.) bacteria. These findings indicate that the presence of the thiazole residue is an essential factor for the antibacterial effect.


Biotechnology & Biotechnological Equipment | 2012

In Vitro Assessment of the Cytotoxic Effects of Sulfo-Arginine Analogues and their Hydrazide Derivatives in 3T3 and HepG2 Cells

Tatyana Dzimbova; Ivan Iliev; K. Georgiev; R. Detcheva; Anelia Balacheva; Tamara Pajpanova

ABSTRACT The cytotoxic activities of sulfo-arginine analogues sArg, NsArg, and their hydrazide derivatives, sArg-CONHNH2, sArg-CONHNC6H5, sArg-CONHN(CH2CH2Cl)2, NsArg-CONHNH2, NsArg-CONHNC6H5, NsArg-CONHN(CH2CH2Cl)2, on 3T3 and HepG2 cells were examined. The substitution in the carboxylic group of sArg increases the cell growth inhibitory effects of the compounds, especially in the case of the bis-(2-chloroethyl)hydrazide substitute. Similar correlation was observed in the case of NsArg and its analogues, but here the most pronounced effect was observed with the analogue NsArg-CONHNH2.


Zeitschrift für Naturforschung C | 2009

Cytotoxic activity of platinum(II) and palladium(II) complexes of N-3-pyridinylmethanesulfonamide: the influence of electroporation.

Nicolay I. Dodoff; Iordan Iordanov; Iana Tsoneva; Konstantin Grancharov; Roumyana Detcheva; Tamara Pajpanova; Martin R. Berger

The series of complexes: cis-[Pd(PMSA)2X2], cis-[Pt(PMSA)2X2], trans-[Pt(PMSA)2I2] and [Pt(PMSA)4]Cl2 (PMSA = N-3-pyridinylmethanesulfonamide; X = Cl, Br, I), previously synthesized and characterized by us, as well as the free ligand PMSA, were tested for their cytotoxic activity without electroporation - against murine leukemia F4N and human SKW-3 and MDA-MB-231 tumour cell lines - and with electroporation - against the latter two cell lines. The majority of the complexes exhibited cytotoxic effects (IC50 < 100 μmol/l) under the conditions of electroporation. Both cis- and trans-[Pt(PMSA)2I2] had pronounced cytotoxic effects (29 - 61 μmol/l against MDA-MB-231 cells).


Medicinal Chemistry Research | 2014

Kyotorphin analogues containing unnatural amino acids: synthesis, analgesic activity and computer modeling of their interactions with μ-receptor

Tatyana Dzimbova; Adriana Bocheva; Tamara Pajpanova

Kyotorphin (KTP; Tyr-Arg) an endogenous neuropeptide is potently analgesic when delivered directly to CNS. An effort to enhance the potency, enzymatic stability and improving bioavailability of KTP is the modification with unnatural amino acids. The aims of presented study were: (1) To synthesize new analogues of kyotorphin containing unnatural amino acids: norcanavaine (NCav) and norcanaline (NCan), structural analogues of arginine and ornithine, respectively; (2) To understand the influence of the arginine mimetics on the pharmacological properties of KTP analogues, through examination their effects on the paw pressure nociceptive threshold; (3) To find relationship between the structure and obtained biological effects of the all synthesized kyotorhin analogues, by molecular docking with μ-opioid receptor. As a result of our work four new kyotorphin analogues containing NCan and NCav were obtained. A correlation between the data from the in vivo test and docking results was found. This allows a better elucidation of the ligand-receptor interactions, the prediction of biological activity of the newly synthesized compounds, and to generate compounds with increased biological effects.


Medicinal Chemistry Research | 2015

MIF-1 and Tyr-MIF-1 analogues containing unnatural amino acids: synthesis, biological activity and docking studies

Rositsa Kalauzka; Tatyana Dzimbova; Adriana Bocheva; Tamara Pajpanova

Melanocyte-inhibiting factor (MIF-1) is the first hypothalamic tripeptide which has been demonstrated to act not only in the brain but also in the pituitary. Tyr-MIF-1 acts as an opiate agonist. It binds selectively and with a high affinity to the μ-opioid receptor when compared with the δ-and κ-opioid receptors. A large number of analogues of MIF-1 and Tyr-MIF-1, containing various modifiers in their structures, have been synthesized and their analgesic effect was determined by various in vivo tests. The aim of current study was: (1) to synthesize new MIF-1 and Tyr-MIF-1 analogues containing sulfoarginine (sArg) and norsulfoarginine (NsArg) in the second and third position, respectively; (2) with the help of docking procedures to find the relationship between structure and biological activity of MIF-1 and Tyr-MIF-1 analogues previously synthesized and biologically tested; (3) using found correlation to predict the biological effect of newly synthesized analogues. New analogues of MIF-1 and Tyr-MIF-1 were synthesized using methods of peptide synthesis in solution. Docking was performed with GOLD 5.0 and a correlation between the obtained docking data and the values from in vivo test was found. Some structure–activity relationships were determined. According to the correlation, we made assumptions about the biological effect of sArg and NsArg containing MIF-1 and Tyr-MIF-1. A computational approach could be very useful in the elucidation of the structure–activity relationship and in the design of new analogues with desired biological effect.

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Tatyana Dzimbova

Bulgarian Academy of Sciences

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Evgeny Golovinsky

Bulgarian Academy of Sciences

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Peter Milanov

Bulgarian Academy of Sciences

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Anelia Balacheva

Bulgarian Academy of Sciences

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Nevena Pencheva

Bulgarian Academy of Sciences

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A. Jordanova

Bulgarian Academy of Sciences

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Konstantin Grancharov

Bulgarian Academy of Sciences

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Nicolay I. Dodoff

Bulgarian Academy of Sciences

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