Jan Barciszewski

Institute of Bioorganic Chemistry Polish Academy of Science, Posen, Greater Poland Voivodeship, Poland

Are you Jan Barciszewski?

Claim your profile

Publications (241)715.17 Total impact

  • ACS Chemical Biology 06/2015; 10(6):1358-61. DOI:10.1021/acschembio.5b00320 · 5.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Malignant gliomas represent the most devastating group of brain tumors in adults, among which glioblastoma multiforme (GBM) exhibits the highest malignancy rate. Despite combined modality treatment, GBM recurs and is invariably fatal. A further insight into the molecular background of gliomagenesis is required to improve patient outcomes. The primary aim of this study was to gain broad information on the miRNA expression pattern in malignant gliomas, mainly GBM. We investigated the global miRNA profile of malignant glioma tissues with miRNA microarrays, deep sequencing and meta-analysis. We selected miRNAs that were most frequently deregulated in glioblastoma tissues, as well as in peritumoral areas, in comparison with normal human brain. We identified candidate miRNAs associated with the progression from glioma grade III to glioma grade IV. The meta-analysis of miRNA profiling studies in GBM tissues summarizes the past and recent advances in the investigation of the miRNA signature in GBM versus noncancerous human brain and provides a comprehensive overview. We propose a list of 35 miRNAs whose expression is most frequently deregulated in GBM patients and of 30 miRNA candidates recognized as novel GBM biomarkers. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
    Molecular oncology 03/2015; DOI:10.1016/j.molonc.2015.03.007 · 5.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genetic transformation of mitochondria in multicellular eukaryotes has remained inaccessible, hindering fundamental investigations and applications to gene therapy or biotechnology. In this context, we have developed a strategy to target nuclear transgene-encoded RNAs into mitochondria in plants. We describe here mitochondrial targeting of trans-cleaving ribozymes destined to knockdown organelle RNAs for regulation studies and inverse genetics and biotechnological purposes. The design and functional assessment of chimeric RNAs combining the ribozyme and the mitochondrial shuttle are detailed, followed by all procedures to prepare constructs for in vivo expression, generate stable plant transformants, and establish target RNA knockdown in mitochondria.
    Methods in molecular biology (Clifton, N.J.) 01/2015; 1265:227-54. DOI:10.1007/978-1-4939-2288-8_17 · 1.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The generally accepted model of the miRNA-guided RNA down-regulation suggests that mature miRNA targets mRNA in a nucleotide sequence-specific manner. However, we have shown that the nucleotide sequence of miRNA is not the only determinant of miRNA specificity. Using specific nucleases, T1, V1 and S1 as well as NMR, UV/Vis and CD spectroscopies, we found that miR-21, miR-93 and miR-296 can adopt hairpin and/or homoduplex structures. The secondary structure of those miRNAs in solution is a function of RNA concentration and ionic conditions. Additionally, we have shown that a formation of miRNA hairpin is facilitated by cellular environment.Looking for functional consequences of this observation, we have perceived that structure of these miRNAs resemble RNA aptamers, short oligonucleotides forming a stable 3D structures with a high affinity and specificity for their targets. We compared structures of anti-tenascin C (anti-Tn-C) aptamers, which inhibit brain tumor glioblastoma multiforme (GBM, WHO IV) and selected miRNA. A strong overexpression of miR-21, miR-93 as well Tn-C in GBM may imply some connections between them. The structural similarity of these miRNA hairpins and anti-Tn-C aptamers indicates that miRNAs may function also beyond RISC and are even more sophisticated regulators, that it was previously expected. We think that the knowledge of the miRNA structure may give a new insight into miRNA-dependent gene regulation mechanism and be a step forward in the understanding their function and involvement in cancerogenesis. This may improve design process of anti-miRNA therapeutics.
    PLoS ONE 11/2014; 9(11):e113848. DOI:10.1371/journal.pone.0113848 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Changes in global 5-methylcytosine amount in Acer platanoides seeds were measured.•Viability of A. platanoides seeds was tested by germination and seedling emergence assays.•Desiccation of A. platanoides seeds causes sine wave-like alterations in m5C amount.•Alterations in m5C amount represent a specific response of orthodox seeds to drying.
    Plant Physiology and Biochemistry 10/2014; DOI:10.1016/j.plaphy.2014.10.014 · 2.35 Impact Factor
  • Jan Barciszewski, Volker A. Erdmann, Eric G. Moss
    [Show abstract] [Hide abstract]
    ABSTRACT: Appreciation is growing for the importance of RNA and its interacting proteins across biology. These molecules function not only in basic cellular processes and the flow of genetic information, but in controlling gene expression, quality control, cell health and development. Yet a full understanding of the signficance of these molecules is only emerging. Genome sequencing has identified numerous RNA-binding proteins whose biological functions are not yet known, as well as many mysterious non-coding RNAs. Importantly, RNA itself is becoming increasingly relevant to disease and its treatment.
    RNA Biology 10/2014; 1(1):1-1. DOI:10.4161/rna.1.1.1006 · 5.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Cu(I) catalyzed Huisgen 1,3-dipolar azide-alkyne cycloaddition (CuAAC) was applied for a nucleoside-peptide bioconjugation. Systemin (Sys), an 18-aa plant signaling peptide naturally produced in response to wounding or pathogen attack, was chemically synthesized as its N-propynoic acid functionalized analog (Prp-Sys) using the SPPS. Next, CuAAC was applied to conjugate Prp-Sys with 3′-azido-2′,3′-dideoxythymidine (AZT), a model cargo molecule. 1,4-Linked 1,2,3-triazole AZT-Sys conjugate was designed to characterize the spreading properties and ability to translocate of cargo molecules of systemin. CuAAC allowed the synthesis of the conjugate in a chemoselective and regioselective manner, with high purity and yield. The presence of Cu(I) ions generated in situ drove the CuAAC reaction to completion within a few minutes without any by-products. Under typical separation conditions of phosphate ‘buffer’ at low pH and uncoated fused bare-silica capillary, an increasing peak intensity assigned to triazole-linked AZT-Sys conjugate was observed using capillary electrophoresis (CE) during CuAAC. CE analysis showed that systemin peptides are stable in tomato leaf extract for up to a few hours. CE-ESI-MS revealed that the native Sys and its conjugate with AZT are translocated through the tomato stem and can be directly detected in stem exudates. The results show potential application of systemin as a transporter of low molecular weight cargo molecules in tomato plant and of CE method to characterize a behavior of plant peptides and its analogs. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
    Journal of Peptide Science 09/2014; 20(9). DOI:10.1002/psc.2653 · 1.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plants respond to environmental changes by modifying gene expression. One of the mechanisms regulating gene expression is methylation of cytosine to 5-methylcytosine (m(5)C) which modulates gene expression by changing chromatin structure. Methylation/demethylation processes affect genes that are controlled upon environmental stresses. Here, on account of the regulatory role of m(5)C, we evaluate the content of m(5)C in DNA from normal and wound-damaged maize leaves. Wounding leads to a transient decrease of the global DNA methylation level ca 20-30% 1 h after the treatment followed by a return to the initial level within the next hours. Similar results were obtained using of radio-labeled nucleotides separated by Thin Layer Chromatography (TLC) or using m(5)C-specific Enzyme-Linked Immunosorbent Assay (ELISA). Wounding induced in maize leaves a two-step oxidative stress, an early one just after wounding and the second two hours later. It coincides with the transient changes of the cytosine methylation level. In the stress-inducible maize calcium-dependent protein kinase ZmCPK11 gene wounding transiently reduced methylation of cytosines 100 and 126 in the first exon.
    Plant Physiology and Biochemistry 06/2014; 82C:202-208. DOI:10.1016/j.plaphy.2014.06.003 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pedunculate oak (Quercus robur) is an ecologically and economically important forest tree species which produces seeds that are classified as recalcitrant. Thus, cryopreservation of seed meristems is a method for long-term preservation of this germplasm in gene banks. During cryopreservation, many factors, such as desiccation, cryoprotection and cooling/rewarming, can induce stress in the frozen meristems. In this study, in vitro survival and the global DNA methylation level of plumules after cryoprotection, desiccation and cryostorage was evaluated. Results indicated that both desiccation and storage in liquid nitrogen have negligible influence on DNA methylation status of Q. robur plumules. These findings support the cryopreservation of plumules as an appropriate method for conservation of Q. robur germplasm.
    Plant Cell Tissue and Organ Culture 04/2014; 117(1). DOI:10.1007/s11240-013-0417-9 · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: With the discovery of small non-coding RNA (ncRNA) molecules as regulators for cellular processes, it became intriguing to develop technologies by which these regulators can be applied in molecular biology and molecular medicine. The application of ncRNAs has significantly increased our knowledge about the regulation and functions of a number of proteins in the cell. It is surprising that similar successes in applying these small ncRNAs in biotechnology and molecular medicine have so far been very limited. The reasons for these observations may lie in the high complexity in which these RNA regulators function in the cells and problems with their delivery, stability and specificity. Recently, we have described mirror-image hammerhead ribozymes and DNAzymes (Spiegelzymes®) which can sequence-specifically hydrolyse mirror-image nucleic acids, such as our mirror-image aptamers (Spiegelmers) discovered earlier. In this paper, we show for the first time that Spiegelzymes are capable of recognising complementary enantiomeric substrates (D-nucleic acids), and that they efficiently hydrolyse them at submillimolar magnesium concentrations and at physiologically relevant conditions. The Spiegelzymes are very stable in human sera, and do not require any protein factors for their function. They have the additional advantages of being non-toxic and non-immunogenic. The Spiegelzymes can be used for RNA silencing and also as therapeutic and diagnostic tools in medicine. We performed extensive three-dimensional molecular modelling experiments with mirror-image hammerhead ribozymes and DNAzymes interacting with D-RNA targets. We propose a model in which L/D-double helix structures can be formed by natural Watson-Crick base pairs, but where the nucleosides of one of the two strands will occur in an anticlinal conformation. Interestingly enough, the duplexes (L-RNA/D-RNA and L-DNA/D-RNA) in these models can show either right- or left-handedness. This is a very new observation, suggesting that molecular symmetry of enantiomeric nucleic acids is broken down.
    PLoS ONE 01/2014; 9(1):e86673. DOI:10.1371/journal.pone.0086673 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of storage and deep desiccation on structural changes of DNA in orthodox seeds are poorly characterized. In this study we analyzed the 5-methylcytosine (m(5)C) global content of DNA isolated from seeds of common pear (Pyrus communis L.) that had been subjected to extreme desiccation, and the seedlings derived from these seeds. Germination and seedling emergence tests were applied to determine seed viability after their desiccation. In parallel, analysis of the global content of m(5)C in dried seeds and DNA of seedlings obtained from such seeds was performed with a 2D TLC method. Desiccation of fresh seeds to 5.3% moisture content (mc) resulted in a slight reduction of DNA methylation, whereas severe desiccation down to 2-3% mc increased DNA methylation. Strong desiccation of seeds resulted in the subsequent generation of seedlings of shorter height. A 1-year period of seed storage induced a significant increase in the level of DNA methylation in seeds. It is possible that alterations in the m(5)C content of DNA in strongly desiccated pear seeds reflect a reaction of desiccation-tolerant (orthodox) seeds to severe desiccation. Epigenetic changes were observed not only in severely desiccated seeds but also in 3-month old seedlings obtained from these seeds. With regard to seed storage practices, epigenetic assessment could be used by gene banks for early detection of structural changes in the DNA of stored seeds.
    PLoS ONE 08/2013; 8(8):e70693. DOI:10.1371/journal.pone.0070693 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hammerhead ribozyme is a versatile tool for down-regulation of gene expression in vivo. Due to its small size and high activity, it is used as a model for RNA structure-function relationship studies. Here we describe a new extended hammerhead ribozyme HH-2 with a tertiary stabilizing motif constructed on the basis of the tetraloop receptor sequence. This ribozyme is very active in living cells but shows low activity in vitro. To understand it, we analyzed tertiary structure models of substrate:ribozyme complexes. We calculated six unique catalytic core geometry parameters as distances and angles between particular atoms that we call the ribozyme fingerprint. A flanking sequence and tertiary motif change the geometry of the general base, general acid, nucleophile and the leaving group. We found almost complete correlation between these parameters and the decrease of target gene expression in the cells. The tertiary structure model calculations allow us to predict ribozyme intracellular activity. Our approach could be widely adapted to characterize catalytic properties of other RNAs.
    Biochemical Journal 02/2013; DOI:10.1042/BJ20121761 · 4.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this manuscript we describe for the first time mirror image catalytic nucleic acids (Spiegelzymes), which hydrolyze sequence specifically L-ribonucleic acid molecules. The mirror image nucleic acid ribozymes designed are based upon the known hammerhead ribozyme and DNAzyme structures that contain L-ribose or L-deoxyribose instead of the naturally occurring D-ribose or D-deoxyribose, respectively. Both Spiegelzymes show similar hydrolytic activities with the same L-RNA target molecules and they also exhibit extra ordinary stabilities when tested with three different human sera. In this respect they are very similar to Spiegelmers (mirror image aptamers), which we had previously developed and for which it has been shown that they are non-toxic and non-immunogenic. Since we are also able to demonstrate that the hammerhead and DNAzyme Spiegelzymes can also hydrolyze mirror image oligonucleotide sequences, like they occur in Spiegelmers, in vivo, it seems reasonable to assume that Spiegelzymes may in principle be used as an antidote against Spiegelmers. Since the Spiegelzymes contain the same building blocks as the Spiegelmers, it can be expected that they will have similar favorable biological characteristics concerning toxicity and immunogenety. In trying to understand the mechanism of action of the Spiegelzymes described in this study, we have initiated for the first time a model building system with L-nucleic acids. The models for L-hammerhead ribozyme and L-DNAzyme interaction with the same L-RNA target will be presented.
    PLoS ONE 01/2013; 8(1):e54741. DOI:10.1371/journal.pone.0054741 · 3.53 Impact Factor
  • Source
    Marta M Gabryelska, Jan Barciszewski
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the key questions of biology is the nature and mechanisms of gene function. It has been 60 years since proposing the right-handed model of DNA double helix in 1953. This discovery was honored with Nobel Prize in 1962 and become a breakthrough in knowing and understanding mechanisms of heredity and genetic code. Since that time a great deal of data have been gathered considering functions, structure and DNA application. It became the basis of modern molecular biology, chemical biology and biotechnology. Today we know, that double helix is characterized by its dynamics and plasticity, which depend on its nucleotide sequence. Chromatin structure and DNA mediated charge transport have a crucial role in understanding mechanisms of its damage and repair. Progress in epigenetics allowed to identify new DNA bases, such as 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine. Design of new catalytic nucleic acids and the nanotechnology field of DNA origami reveal its application potential.
    Postepy biochemii 01/2013; 59(3):246-56.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hammerhead ribozyme is the smallest naturally occurring catalytic RNA. It is a perfect model for structure-function relation studies. Initially, it was identified as an autocatalytic part of viroid and virusoid genomic RNA. It exists within the genomes of many organisms including human, which makes it the most common autocatalytic motif in the nature. After 25 years of intensive research, there are a lot of data considering its structure, conformational dynamics and an influence of tertiary stabilizing motifs on its stability and properties. Structure of the hammerhead ribozyme is a system of elements that influence each other. The knowledge of ribozyme architecture is outstandingly interesting in the context of rules and logic of design, construction and application of such molecules as spatial molecular constructions. Presence of additional structural motifs distinguishes extended hammerhead ribozyme from the minimal one. Hammerhead ribozyme recognizes complementary RNA and catalyses transesterification after the 5'-NUH-3' sequence. Reaction efficiency depends on an arrangement of atoms of the catalytic core presence of metal ions and other intracellular factors. Innovative and potentially better derivatives of the hammerhead ribozyme are objects of extensive research in the field of molecular medicine.
    Postepy biochemii 01/2013; 59(1):22-32.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Convenient and efficient methods of the synthesis of N(6)- and N(4)-substituted derivatives of adenine and cytosine and their 2'-deoxyribosides were developed. The reactions of either unprotected nucleobases (adenine, cytosine) or unprotected 2'-deoxyribosides with aryl or alkyl aldehydes give corresponding Schiff bases that can be reduced to the target title compounds with high overall yields. In the case of aryl aldehydes the imine derivatives are obtained in the presence of methoxides in methanol and reduced with sodium borohydride. The corresponding reactions with alkyl aldehydes require the use of acetic acid and borane dimethyl sulfide complex instead.
    Nucleosides Nucleotides &amp Nucleic Acids 12/2012; 31(12):861-871. DOI:10.1080/15257770.2012.742198 · 0.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate the effect of phloretamide (PA), an apple constituent, on the activation of the Nrf2 transcription factor and the expression of its target genes: glutathione S-transferases (GSTs), NAD(P)H:quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) in normal human THLE-2 hepatocytes and the hepatoma HepG2 cell line. PA did not show significant cytotoxicity towards THLE-2 cells but such an effect was observed in HepG2 cells (IC(50) ∼200μM). The treatment of cells with PA resulted in the translocation of Nrf2 from cytosol to nucleus in both cell lines, but increased the level of its transcript and protein only in THLE-2 cells. In this cell line an increased level of GSTA, GSTP, GSTT, NQO1 mRNA was also observed. Increased expression of GSTs was confirmed by enhancement of their protein levels. The increase in p53 protein content observed in THLE-2 may be associated with its stabilization induced by the enhancement of NQO1 level. PA did not affect Nrf2, GSTs, NQO1 or HO-1 expression in HepG2 cells. These results suggest that PA has rather chemopreventive than chemiotherapeutic potential and acts similarly as apple dihydrochalcones through the induction of detoxification/antioxidative enzymes.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 10/2012; 51. DOI:10.1016/j.fct.2012.09.033 · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DNA cytosine methylation catalyzed by DNA methyltransferase 1 (DNMT1) is an epigenetic method of gene expression regulation and development. Changes in methylation pattern lead to carcinogenesis. Inhibition of DNMT1 activity could be a good strategy of safe and efficient epigenetic therapy. In this work, we present a novel group of cytosine analogs as inhibitors of DNA methylation. We show new methods of synthesis and their effect on in vitro reaction of DNA methylation. Almost all of analyzed compounds inhibit DNA methyltransferase activity in the competitive manner. K(i) values for the most potent compound 4-N-furfuryl-5,6-dihydroazacytosines is 0.7 μM. These compounds cause also a decrease of 5-methylcytosine (m(5)C) level in DNA of mammalian HeLa and HEK293 cells.
    European Journal of Medicinal Chemistry 07/2012; 55:243-54. DOI:10.1016/j.ejmech.2012.07.024 · 3.43 Impact Factor
  • Volker A. Erdmann, Jan Barciszewski
    ChemInform 02/2012; 43(8). DOI:10.1002/chin.201208269
  • Source
    Małgorzata Giel-Pietraszuk, Jan Barciszewski
    [Show abstract] [Hide abstract]
    ABSTRACT: The tertiary structure of nucleic acids results from an equilibrium between electrostatic interactions of phosphates, stacking interactions of bases, hydrogen bonds between polar atoms and water molecules. Water interactions with ribonucleic acid play a key role in its structure formation, stabilization and dynamics. We used high hydrostatic pressure and osmotic pressure to analyze changes in RNA hydration. We analyzed the lead catalyzed hydrolysis of tRNAPhe from S. cerevisiae as well as hydrolytic activity of leadzyme. Pb(II) induced hydrolysis of the single phosphodiester bond in tRNAPhe is accompanied by release of 98 water molecules, while other molecule, leadzyme releases 86.
    Molecular Biology Reports 02/2012; 39(5):6309-18. DOI:10.1007/s11033-012-1452-z · 1.96 Impact Factor

Publication Stats

2k Citations
715.17 Total Impact Points


  • 1981–2015
    • Institute of Bioorganic Chemistry Polish Academy of Science
      Posen, Greater Poland Voivodeship, Poland
  • 2001–2014
    • Polish Academy of Sciences
      • Institute of Organic Chemistry
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1987–2013
    • Instytut Historii Polskiej Akademii Nauk
      Posen, Greater Poland Voivodeship, Poland
  • 2007–2012
    • Instytut Matki i Dziecka
      Warszawa, Masovian Voivodeship, Poland
    • BioInfoBank Institute
      Posen, Greater Poland Voivodeship, Poland
  • 2011
    • Społeczna Akademia Nauk
      Warszawa, Masovian Voivodeship, Poland
  • 2010
    • Gdansk University of Technology
      Danzig, Pomeranian Voivodeship, Poland
  • 1997–2008
    • Freie Universität Berlin
      • Institute of Chemistry and Biochemistry
      Berlin, Land Berlin, Germany
    • Medical University of Gdansk
      • Department of Pharmacology
      Gdańsk, Pomeranian Voivodeship, Poland
  • 2005–2006
    • Poznan University of Medical Sciences
      • Department of Neurosurgery and Neurotraumatology
      Posen, Greater Poland Voivodeship, Poland
  • 1999–2000
    • Hebrew University of Jerusalem
      • Department of Biological Chemistry
      Yerushalayim, Jerusalem, Israel
  • 1995–1999
    • University of Gdansk
      • Faculty of Chemistry
      Danzig, Pomeranian Voivodeship, Poland
    • Instytut Chemii Fizycznej PAN
      Warszawa, Masovian Voivodeship, Poland
  • 1993
    • Aarhus University
      • Department of Chemistry
      Aars, Region North Jutland, Denmark
  • 1991
    • Yale University
      • Department of Molecular Biophysics and Biochemistry
      New Haven, Connecticut, United States
  • 1990
    • Adam Mickiewicz University
      Posen, Greater Poland Voivodeship, Poland
  • 1985
    • University of Zurich
      Zürich, Zurich, Switzerland