A5070079600- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- Synthesis and Characterization of Heterocyclic Compounds
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- Carbohydrate Chemistry and Synthesis
- Polyamine Metabolism and Applications
- Photochemistry and Electron Transfer Studies
- Enzyme Structure and Function
- Synthesis and Biological Evaluation
- Synthesis and Reactions of Organic Compounds
- Cytomegalovirus and herpesvirus research
- Liquid Crystal Research Advancements
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Fluorine in Organic Chemistry
- Trypanosoma species research and implications
- Chemical Reaction Mechanisms
- Porphyrin and Phthalocyanine Chemistry
- Photoreceptor and optogenetics research
- Adenosine and Purinergic Signaling
University of Warsaw
2005-2020
Institute of Experimental Physics of the Slovak Academy of Sciences
1977-2016
Lodz University of Technology
2005-2013
Polish Academy of Sciences
2004-2011
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
1978-2008
Institute of Physics
2004-2008
Louisiana State University Health Sciences Center Shreveport
2004
McGill University
2002
University Medical Center
1999
University Hospital and Clinics
1999
Synthetic analogs of the 5′-terminal caps eukaryotic mRNAs and snRNAs are used in elucidating such physiological processes as mRNA translation, pre-mRNA splicing, intracellular transport snRNAs, turnover. Particularly useful RNAs capped with synthetic analogs, which produced by vitro transcription a DNA template using bacteriophage RNA polymerase presence ribonucleoside triphosphates cap dinucleotide m 7 Gp 3 G. Unfortunately, because 3′-OH on both Guo moieties, up to half contain...
Initiation factor 4E (eIF-4E) binds to the m7GTP-containing cap of eukaryotic mRNA and facilitates entry into initiation cycle protein synthesis. eIF-4E is a phosphoprotein, phosphorylated form caps 3-4-fold more tightly than nonphosphorylated form. A previous study indicated that major phosphorylation site was Ser-53 (Rychlik, W., Russ, M. A., Rhoads, R. E.(1987) J. Biol. Chem. 262, 10434-10437). In present study, we synthesized phosphopeptide expected result from tryptic digestion eIF-4E,...
Phosphorylation of the eukaryotic initiation factor eIF4E in response to mitogenic stimuli and cytokines is implicated regulation step translation. It still remains unclear how phosphorylation regulates To address this problem, we applied a unique technique protein engineering, intein-mediated ligation, synthesize eIF4E, which selectively phosphorylated at Ser 209. Using chosen synthetic cap analogs, compared quantitatively affinity for unphosphorylated by fluorometric time-synchronized...
Fifty-eight analogues of the 5'-terminal 7-methylguanosine-containing cap eukaryotic messenger RNA were synthesized and tested for their ability to inhibit in vitro protein synthesis. A new algorithm was developed extracting KI, dissociation constant analogue·eIF4E complex, from synthesis data. The results indicated that addition a methyl group N2 guanine produced more inhibitory compounds, but second decreased level inhibition dramatically. Aryl substitution at N7 improved efficacy...
The syn ⇄ anti equilibrium conformation about the glycosidic bond of purine nucleosides and 5′‐nucleotides in different solvent systems has been investigated by means 1 H NMR spectroscopy. Quantitative values for conformer populations were improved, relative to previous results, a detailed study of, resultant derived correction for, influence sugar exocyclic group on chemical shifts ring protons. This was achieved with aid nucleotides fixed conformations gauche‐trans [derivatives 8,5′‐( R...
Synthetic analogs of the N7-methylated guanosine triphosphate cap at 5′ end eukaryotic mRNAs and snRNAs have played an important role in understanding their splicing, intracellular transport, translation, turnover. We report here a new series N7-benzylated dinucleoside tetraphosphate analogs, b 7 Gp 4 G, m 3′- O 2 that extend our knowledge translation. used these novel along with 10 previously synthesized to explore five parameters: binding affinity eIF4E, inhibition cap-dependent...
The rate-limiting step for cap-dependent translation initiation in eukaryotes is recruitment of mRNA to the ribosome. An early event this process recognition m<sup>7</sup>GTP-containing cap structure at 5′-end by factor eIF4E. In nematode <i>Caenorhabditis elegans</i>, mRNAs from 70% genes contain a different structure, m<sub>3</sub><sup>2,2,7</sup>GTP. This poorly recognized mammalian elF4E, suggesting that <i>C. elegans</i>may possess specialized form elF4E can recognize Analysis...
Specific recognition of the mRNA 5' cap by eukaryotic initiation factor eIF4E is a rate-limiting step in translation initiation. Fluorescence spectroscopy and high-sensitivity isothermal titration calorimetry were used to examine thermodynamics binding cap-analogue, 7-methylGpppG. A van't Hoff plot revealed nonlinearity characterized an unexpected, large positive molar heat capacity change ( = +1.92 ± 0.93 kJ·mol-1·K-1), which was confirmed direct ITC measurements +1.941 0.059 kJ·mol-1·K-1)....
Eukaryotic translation initiation factor 4E (eIF4E) is essential for efficient protein synthesis in cap-dependent translation. The specifically binds the cap structure at mRNA 5' terminus and facilitates assembly of with other factors 40S ribosomal subunit. Phosphorylation eIF4E implicated regulation step However, molecular mechanism this still remains unclear. To address problem, we have determined binding affinities mutated position 209 or 159 a series novel mono- dinucleotide analogues by...
The heterodimeric nuclear cap-binding complex (CBC) binds to the mono-methylated 5′ cap of eukaryotic RNA polymerase II transcripts such as mRNA and U snRNA. binding is important for maturation mRNAs possibly in first round translation nonsense-mediated decay. It also essential export snRNAs metazoans. We report characterization by fluorescence spectroscopy recognition capped human CBC. association constants ( K ) 17 mono- dinucleotide analogs well oligomer m 7 GpppA m2′ pU pA cover range...
Metazoan spliced leader (SL) trans -splicing generates mRNAs with an m 2,2,7 G-cap and a common downstream SL RNA sequence. The mechanism for eIF4E binding is unknown. Here, we describe the first structure of compare it to cognate 7 G-eIF4E complex. These structures Nuclear Magnetic Resonance (NMR) data indicate that nematode Ascaris suum binds two different caps in similar manner except loss single hydrogen bond on G-cap. Nematode mammalian both have low affinity compared G-cap, G-SL 22-nt...
Abstract P1,P3−Dinucleoside triphosphates, N(5′)G(5′)G, have been prepared in which N is 7-Me-, 7-Et-, 7-Bn, N2, 7-diMe- or N2,N2, 7-triMe-guanosine. Conformations of the nucleoside moieties determined and compared with those corresponding monophosphates. The hydrolytic stability 7-alkylguanine ring has studied origin structural effects elucidated by comparative kinetic studies monomeric nucleotide analogs. mechanism alkaline decomposition established Or following cleavage 7-methylguanosine...
Analyses of 1 H and 13 C NMR spectra have been utilized to extend studies on the dynamic equilibrium syn–anti about glycosidic bond purine nucleosides nucleotides. With aid chemically synthesized model analogous in fixed syn anti conformations, introduction appropriate corrections for conformation exocyclic chain sugar moiety, it is possible evaluate quantitatively relative populations conformers from experimentally observed chemical shifts H(2′) C(2′). The resulting agreement between data...
Abstract Chemically synthesized dinucleoside P1, P2-di-, P3-tri- and P4-tetraphosphates, derivatives of 5′-linked 7-methylguanosine guanosine were characterized with respect to their structural properties functional effect on eukaryotic translation inhibition.
Translation of mRNA in eukaryotes begins with specific recognition the 5' cap structure by highly conserved protein, eIF4E. The thermodynamics eIF4E interaction nine chemical analogues has been studied means emission spectroscopy. High-sensitivity measurements intrinsic protein fluorescence quenching upon binding provided equilibrium association constants temperature range 279 to 314 K. A van't Hoff analysis yielded negative enthalpies for entire analogue series, −16.6 −81 kJ mol-1, and...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution structure of the EcoRI DNA octamer containing 5-fluorouracil via restrained molecular dynamics using distance and torsion angle constraints extracted from NMR spectral simulationsRyszard Stolarski, William Egan, Thomas L. JamesCite this: Biochemistry 1992, 31, 7027–7042Publication Date (Print):August 11, 1992Publication History Published online1 May 2002Published inissue 11 August...
The eukaryotic initiation factor eIF4E binds the mRNA 5′ cap structure and has a central role during translational initiation. mechanisms to control its activity have oncogenic properties thus become targets for anticancer drug development. A recent study (Kentsis et al. 2004) presented evidence that antiviral nucleoside ribavirin phosphorylated derivatives were structural mimics of cap, high-affinity ligands eIF4E, potent repressors eIF4E-mediated cell transformation tumor growth. Based on...