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A. J. W. G. Visser - One of the best experts on this subject based on the ideXlab platform.
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maximum entropy analysis of polarized fluorescence decay of e gfp in aqueous solution
Methods and Applications in Fluorescence, 2017Co-Authors: Victor V Skakun, Eugene Novikov, Jan Willem Borst, A. J. W. G. VisserAbstract:The maximum entropy method (MEM) was used for the analysis of polarized fluorescence decays of enhanced green fluorescent protein (EGFP) in buffered water/glycerol mixtures, obtained with Time-correlated single-photon counting (Visser et al 2016 Methods Appl. Fluoresc. 4 035002). To this end, we used a general-purpose software module of MEM that was earlier developed to analyze (complex) laser photolysis kinetics of ligand rebinding reactions in oxygen binding proteins. We demonstrate that the MEM software provides reliable results and is easy to use for the analysis of both total fluorescence decay and fluorescence anisotropy decay of aqueous solutions of EGFP. The Rotational Correlation Times of EGFP in water/glycerol mixtures, obtained by MEM as maxima of the Correlation-Time distributions, are identical to the single Correlation Times determined by global analysis of parallel and perpendicular polarized decay components. The MEM software is also able to determine homo-FRET in another dimeric GFP, for which the transfer Correlation Time is an order of magnitude shorter than the Rotational Correlation Time. One important advantage utilizing MEM analysis is that no initial guesses of parameters are required, since MEM is able to select the least correlated solution from the feasible set of solutions.
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green fluorescent protein from the bioluminescent jellyfish clytia gregaria is an obligate dimer and does not form a stable complex with the ca2 discharged photoprotein clytin
Biochemistry, 2011Co-Authors: Natalia P Malikova, Victor V Skakun, Nina V Visser, Arie Van Hoek, Eugene S Vysotski, John G Lee, A. J. W. G. VisserAbstract:Green-fluorescent protein (GFP) is the origin of the green bioluminescence color exhibited by several marine hydrozoans and anthozoans. The mechanism is believed to be Forster resonance energy transfer (FRET) within a luciferase−GFP or photoprotein−GFP complex. As the effect is found in vitro at micromolar concentrations, for FRET to occur this complex must have an affinity in the micromolar range. We present here a fluorescence dynamics investigation of the recombinant bioluminescence proteins from the jellyfish Clytia gregaria, the photoprotein clytin in its Ca2+-discharged form that is highly fluorescent (λmax = 506 nm) and its GFP (cgreGFP; λmax = 500 nm). Ca2+-discharged clytin shows a predominant fluorescence lifeTime of 5.7 ns, which is assigned to the final emitting state of the bioluminescence reaction product, coelenteramide anion, and a fluorescence anisotropy decay or Rotational Correlation Time of 12 ns (20 °C), consistent with tight binding and rotation with the whole protein. A 34 ns correl...
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effects of refractive index and viscosity on fluorescence and anisotropy decays of enhanced cyan and yellow fluorescent proteins
Journal of Fluorescence, 2005Co-Authors: Jan Willem Borst, A. J. W. G. Visser, Arie Van Hoek, Mark A HinkAbstract:The fluorescence lifeTime strongly depends on the immediate environment of the fluorophore. Time-resolved fluorescence measurements of the enhanced forms of ECFP and EYFP in water-glycerol mixtures were performed to quantify the effects of the refractive index and viscosity on the fluorescence lifeTimes of these proteins. The experimental data show for ECFP and EYFP two fluorescence lifeTime components: one short lifeTime of about 1 ns and a longer lifeTime of about 3.7 ns of ECFP and for EYFP 3.4. The fluorescence of ECFP is very heterogeneous, which can be explained by the presence of two populations: a conformation (67% present) where the fluorophore is less quenched than in the other conformation (33% present). The fluorescence decay of EYFP is much more homogeneous and the amplitude of the short fluorescence lifeTime is about 5%. The fluorescence anisotropy decays show that the Rotational Correlation Time of both proteins scales with increasing viscosity of the solvent similarly as shown earlier for GFP. The Rotational Correlation Times are identical for ECFP and EYFP, which can be expected since both proteins have the same shape and size. The only difference observed is the slightly lower initial anisotropy for ECFP as compared to the one of EYFP.
Joop A Peters - One of the best experts on this subject based on the ideXlab platform.
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a gadolinium iii complex of a carboxylic phosphorus acid derivative of diethylenetriamine covalently bound to inulin a potential macromolecular mri contrast agent
Bioconjugate Chemistry, 2004Co-Authors: Petra Lebduskova, Jan Kotek, Petr Hermann, Ivan Lukeš, Luce Vander Elst, Robert N. Muller, Joop A PetersAbstract:A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P−O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifeTime of this water molecule (170 ns at 298 K), a relatively long Rotational Correlation Time (866 ps at 298 K), and the presence of two water molecules in ...
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a gadolinium iii complex of a carboxylic phosphorus acid derivative of diethylenetriamine covalently bound to inulin a potential macromolecular mri contrast agent
Bioconjugate Chemistry, 2004Co-Authors: Petra Lebduskova, Jan Kotek, Petr Hermann, Ivan Lukeš, Luce Vander Elst, Robert N. Muller, Joop A PetersAbstract:A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifeTime of this water molecule (170 ns at 298 K), a relatively long Rotational Correlation Time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.
Peter Caravan - One of the best experts on this subject based on the ideXlab platform.
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hexameric mn ii dendrimer as mri contrast agent
Chemistry: A European Journal, 2014Co-Authors: Eric M Gale, Jiang Zhu, Iliyana P Atanasova, Tyson A Rietz, Peter CaravanAbstract:A Mn(II) chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine-derived [Mn(EDTA)(H2O)]2− moieties coupled to a cyclotriphosphazene core. Variable temperature 17O NMR revealed a single water co-ligand per Mn(II) that undergoes fast water exchange (kex = (3.0±0.1) × 108 s−1 at 37 °C). The 37 °C per Mn(II) relaxivity ranged from 8.2 to 3.8 mM−1s−1 from 0.47 to 11.7T, and is 6-fold higher on a per molecule basis. From this field dependence a Rotational Correlation Time was estimated as 0.45±0.02 ns. The imaging and pharmacokinetic properties of the dendrimer were compared to clinically used [Gd(DTPA)(H2O)]2− in mice at 4.7T. On first pass, the higher per ion relaxivity of the dendrimer resulted in 2-fold greater blood signal than for [Gd(DTPA)(H2O)]2−. Blood clearance was fast and elimination occurred through both the renal and hepatobiliary routes. This Mn(II) containing dendrimer represents potential alternative to Gd-based contrast agents, especially in patients with chronic kidney disease where the use of current Gd-based agents may be contraindicated.
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influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium and manganese based t1 contrast agents
Contrast Media & Molecular Imaging, 2009Co-Authors: Peter Caravan, Christian T Farrar, Luca Frullano, Ritika UppalAbstract:Simulations were performed to understand the relative contributions of molecular parameters to longitudinal (r1) and transverse (r2) relaxivity as a function of applied field, and to obtain theoretical relaxivity maxima over a range of fields to appreciate what relaxivities can be achieved experimentally. The field-dependent relaxivities of a panel of gadolinium and manganese complexes with different molecular parameters, water exchange rates, Rotational Correlation Times, hydration state, etc. were measured to confirm that measured relaxivities were consistent with theory. The design tenets previously stressed for optimizing r1 at low fields (very slow Rotational motion; chelate immobilized by protein binding; optimized water exchange rate) do not apply at higher fields. At 1.5T and higher fields, an intermediate Rotational Correlation Time is desired (0.5–4 ns), while water exchange rate is not as critical to achieving a high r1. For targeted applications it is recommended to tether a mulTimer of metal chelates to a protein-targeting group via a long flexible linker to decouple the slow motion of the protein from the water(s) bound to the metal ions. Per ion relaxivities of 80, 45, and 18 mM−1 s−1 at 1.5, 3 and 9.4 T, respectively, are feasible for Gd3+ and Mn2+ complexes. Copyright © 2009 John Wiley & Sons, Ltd.
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influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium and manganese based t1 contrast agents
Contrast Media & Molecular Imaging, 2009Co-Authors: Peter Caravan, Christian T Farrar, Luca Frullano, Ritika UppalAbstract:Simulations were performed to understand the relative contributions of molecular parameters to longitudinal (r(1)) and transverse (r(2)) relaxivity as a function of applied field, and to obtain theoretical relaxivity maxima over a range of fields to appreciate what relaxivities can be achieved experimentally. The field-dependent relaxivities of a panel of gadolinium and manganese complexes with different molecular parameters, water exchange rates, Rotational Correlation Times, hydration state, etc. were measured to confirm that measured relaxivities were consistent with theory. The design tenets previously stressed for optimizing r(1) at low fields (very slow Rotational motion; chelate immobilized by protein binding; optimized water exchange rate) do not apply at higher fields. At 1.5 T and higher fields, an intermediate Rotational Correlation Time is desired (0.5-4 ns), while water exchange rate is not as critical to achieving a high r(1). For targeted applications it is recommended to tether a mulTimer of metal chelates to a protein-targeting group via a long flexible linker to decouple the slow motion of the protein from the water(s) bound to the metal ions. Per ion relaxivities of 80, 45, and 18 mM(-1) s(-1) at 1.5, 3 and 9.4 T, respectively, are feasible for Gd(3+) and Mn(2+) complexes.
Ritika Uppal - One of the best experts on this subject based on the ideXlab platform.
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influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium and manganese based t1 contrast agents
Contrast Media & Molecular Imaging, 2009Co-Authors: Peter Caravan, Christian T Farrar, Luca Frullano, Ritika UppalAbstract:Simulations were performed to understand the relative contributions of molecular parameters to longitudinal (r1) and transverse (r2) relaxivity as a function of applied field, and to obtain theoretical relaxivity maxima over a range of fields to appreciate what relaxivities can be achieved experimentally. The field-dependent relaxivities of a panel of gadolinium and manganese complexes with different molecular parameters, water exchange rates, Rotational Correlation Times, hydration state, etc. were measured to confirm that measured relaxivities were consistent with theory. The design tenets previously stressed for optimizing r1 at low fields (very slow Rotational motion; chelate immobilized by protein binding; optimized water exchange rate) do not apply at higher fields. At 1.5T and higher fields, an intermediate Rotational Correlation Time is desired (0.5–4 ns), while water exchange rate is not as critical to achieving a high r1. For targeted applications it is recommended to tether a mulTimer of metal chelates to a protein-targeting group via a long flexible linker to decouple the slow motion of the protein from the water(s) bound to the metal ions. Per ion relaxivities of 80, 45, and 18 mM−1 s−1 at 1.5, 3 and 9.4 T, respectively, are feasible for Gd3+ and Mn2+ complexes. Copyright © 2009 John Wiley & Sons, Ltd.
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influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium and manganese based t1 contrast agents
Contrast Media & Molecular Imaging, 2009Co-Authors: Peter Caravan, Christian T Farrar, Luca Frullano, Ritika UppalAbstract:Simulations were performed to understand the relative contributions of molecular parameters to longitudinal (r(1)) and transverse (r(2)) relaxivity as a function of applied field, and to obtain theoretical relaxivity maxima over a range of fields to appreciate what relaxivities can be achieved experimentally. The field-dependent relaxivities of a panel of gadolinium and manganese complexes with different molecular parameters, water exchange rates, Rotational Correlation Times, hydration state, etc. were measured to confirm that measured relaxivities were consistent with theory. The design tenets previously stressed for optimizing r(1) at low fields (very slow Rotational motion; chelate immobilized by protein binding; optimized water exchange rate) do not apply at higher fields. At 1.5 T and higher fields, an intermediate Rotational Correlation Time is desired (0.5-4 ns), while water exchange rate is not as critical to achieving a high r(1). For targeted applications it is recommended to tether a mulTimer of metal chelates to a protein-targeting group via a long flexible linker to decouple the slow motion of the protein from the water(s) bound to the metal ions. Per ion relaxivities of 80, 45, and 18 mM(-1) s(-1) at 1.5, 3 and 9.4 T, respectively, are feasible for Gd(3+) and Mn(2+) complexes.
Lothar Helm - One of the best experts on this subject based on the ideXlab platform.
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nuclear spin relaxation parameters of mri contrast agents insight from quantum mechanical calculations
ChemInform, 2008Co-Authors: Oleg V Yazyev, Lothar HelmAbstract:Nuclear magnetic relaxation in the presence of paramagnetic centres has gained increasing interest in recent years partly due to its importance for contrast agents in magnetic resonance imaging. Rational design of new more efficient agents is possible as a result of a better understanding of the underlying relaxation mechanisms. Quantum chemical calculations together with molecular dynamics simulations allow obtaining fundamental parameters such as quadrupole coupling constants and hyperfine interaction tensors directly at a molecular level. Recent results are presented on gadolinium(III) ions in aqueous solution and on [Gd(DOTA)(H2O)]–, a commercial MRI contrast agent. Isotropic hyperfine coupling constants can be calculated for 17O and 1H nuclear spins of water molecules in the first and second coordination sphere of Gd3+. It is also shown that the commonly used point-dipole approximation for the dipolar interaction between the electron and the nuclear spin is in general valid for 1H spin but not for the directly bound 17O spin. The calculated quadrupole coupling parameters allow a direct determination of the Rotational Correlation Time of complexes from the 17O nuclear spin relaxation.
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17o nuclear quadrupole coupling constants of water bound to a metal ion a gadolinium iii case study
Journal of Chemical Physics, 2006Co-Authors: Oleg V Yazyev, Lothar HelmAbstract:Rotational Correlation Times of metal ion aqua complexes can be determined from O17 NMR relaxation rates if the quadrupole coupling constant of the bound water oxygen-17 nucleus is known. The Rotational Correlation Time is an important parameter for the efficiency of Gd3+ complexes as magnetic resonance imaging contrast agents. Using a combination of density functional theory with classical and Car-Parrinello molecular dynamics simulations we performed a computational study of the O17 quadrupole coupling constants in model aqua ions and the [Gd(DOTA)(H2O)]− complex used in clinical diagnostics. For the inner sphere water molecule in the [Gd(DOTA)(H2O)]− complex the determined quadrupole coupling parameter χ1+η2∕3 of 8.7MHz is very similar to that of the liquid water (9.0MHz). Very close values were also predicted for the the homoleptic aqua ions of Gd3+ and Ca2+. We conclude that the O17 quadrupole coupling parameters of water molecules coordinated to closed shell and lanthanide metal ions are similar to ...
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water soluble gadofullerenes toward high relaxivity ph responsive mri contrast agents
Journal of the American Chemical Society, 2005Co-Authors: Éva Tóth, Lothar Helm, Robert D Bolskar, Alain Borel, Gabriel Gonzalez, Andre E Merbach, Balaji Sitharaman, Lon J WilsonAbstract:The water-soluble endohedral gadofullerene derivatives, Gd@C60(OH)x and Gd@C60[C(COOH)2]10, have been characterized with regard to their MRI contrast agent properties. Water-proton relaxivities have been measured in aqueous solution at variable temperature (278−335 K), and for the first Time for gadofullerenes, relaxivities as a function of magnetic field (5 × 10-4 to 9.4 T; NMRD profiles) are also reported. Both compounds show relaxivity maxima at high magnetic fields (30−60 MHz) with a maximum relaxivity of 10.4 mM-1 s-1 for Gd@C60[C(COOH)2]10 and 38.5 mM-1 s-1 for Gd@C60(OH)x at 299 K. Variable-temperature, transverse and longitudinal 17O relaxation rates, and chemical shifts have been measured at three magnetic fields (B = 1.41, 4.7, and 9.4 T), and the results point exclusively to an outer sphere relaxation mechanism. The NMRD profiles have been analyzed in terms of slow Rotational motion with a long Rotational Correlation Time calculated to be τR298 = 2.6 ns. The proton exchange rate obtained for Gd...
