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Targeted MRI
Published in Robert J. Gropler, David K. Glover, Albert J. Sinusas, Heinrich Taegtmeyer, Cardiovascular Molecular Imaging, 2007
Susan B. Yeon, Andrea J. Wiethoff, Warren J. Manning, Elmar Spuentrup, Rene M. Botnar
The rotational correlation time (τR) is ~0.1 ns for approved agents. Since increases in τR enhance relaxivity, various efforts in contrast agent design have focused on increasing this parameter. TR is lengthened by formation of conjugates between the metal ion complex and slowly moving structures such as proteins, polymers or dendrimers.
Physicochemical Principles of MR Contrast Agents
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Figure 2.3 also shows that the relaxivity is rather field independent for Gd-DTPA and MS-325 in buffer, but the relaxivity of MS-325 bound to protein first increases and then decreases with field. At high fields, the inequality ωH2τc2 > 1 is reached and T1m will become longer (and relaxivity lower) with increasing field. The relaxivity first increases because the correlation time can also change with field. At low fields, electronic relaxation is very fast and the correlation time, τc, is approximately T1e. The electronic relaxation rate for Gd(III) and Mn(II) decreases with the square of the magnetic field, so as field is increased, τc is getting longer and relaxivity increases. At some point, the rate of rotational diffusion is the fastest process and τc becomes τR. The field at which T1e no longer dominates the correlation time will depend on the complex and the rotational correlation time. However, it appears safe to say that at 1.5 tesla and above, rotational motion is the correlation time that defines relaxivity.
Electron Spin Resonance Spectroscopy
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
George C. Yang, Adorjan Aszalos
The rotational correlation time is an approximate measure of the time required for the nitroxide to tumble through an arc of 1 rad. It can be related to the viscosity of lipids by the Stokes relation. Since viscosity and fluidity are universely related, 1/τi can be defined as fluidity. The order parameter S in Equation (1) can be calculated with the following equation where A∥ = 1/2 AmaxA⊥ = 1/2 Amin + 0.86Amax, Amin = hyperfine splitting, shown in Figure 9Axx, Ayy = principle elements of the A tensor. A listing of A tensors for the various spin labels has been compiled by Berliner [38], Experimentally, a 3.3 to 6.6 x 10-8 M solution of a spin label, such as 5-nitroxylstearic acid in 10–20 µl EtOH in a glass tube is evaporated to dryness in vacuum; this residue can be stored at 5°C for many weeks. A cell suspension containing 106 cell in 0.1–0.2 ml phosphate buffered saline solution (pH = 7.2) is pipetted into this glass tube. Capillary tubes or flat cells are used for ESR measurement. In studying the effect of drugs on membrane fluidity, a particular drug will be added to the cell suspension buffer prior to ESR measurement. As a typical example, myocardial cells (106) treated with 10 p g of the polyene antibiotic nystatin introduces a 1.6 G increase in the 2T∥ value (Figure 10), indicating that intercalation of nystatin into the membrane results in a less fluid environment for the spin label [39]. Using the same technique, with the addition of 1.5 µg of adriamycin, results in a more rigid myocardial membrane, as indicated in an increase of about 2G in 2T∥ splitting. Order parameter calculations indicate membrane fluidity changes, reflecting the increase in the 2T∥ values when myocardial cells are treated by these two antibiotics (Figure 9). These spectra were obtained using 5-nitroxylstearic acid spin label.
Investigating protein–excipient interactions of a multivalent VHH therapeutic protein using NMR spectroscopy
Published in mAbs, 2022
Jainik Panchal, Bradley T. Falk, Valentyn Antochshuk, Mark A. McCoy
The use of the R1*R2 parameter is an example of factoring viscosity out of relaxation data to better understand the underlying motions. Another approach is to use the viscosity dependence in the diffusion data to calculate the expected effect of sucrose viscosity on protein NMR R2 rates. If the MV-VHH R2 rate is influenced primarily by rotational diffusion (tumbling), then R2 ~ ητc, where η is the solution viscosity and τc is the rotational correlation time; viscosity (η) can be measured directly by diffusion NMR or by viscometry. In Figure 7, experimental measurement of MV-VHH R2 values (●) as a function of sucrose concentration are shown to be significantly lower than those derived from applying a simple viscosity correction factor to the data without sucrose (line). The significant differences can be accounted for by changes in internal motions that reduced ms-μ
Interaction of Alpha-Crystallin with Phospholipid Membranes
Published in Current Eye Research, 2021
Laxman Mainali, William J. O’Brien, Raju Timsina
The spin-lattice relaxation rate (T1−1) obtained from the SR EPR measurements of lipid spin labels in deoxygenated samples depends primarily on the rotational correlation time of the nitroxide moiety within the lipid bilayer.60,61 Thus, T1−1 can be used as a convenient quantitative measure of membrane fluidity that reflects the local motional properties of the lipid alkyl chain.59,62-65 Previously, we have used T1−1 as a convenient quantitative measure of fluidity using phospholipid analog (n-PC, 9-SASL) and cholesterol analog (CSL) spin labels in model and eye lens lipid membranes.53,59,62-66 Representative saturation recovery EPR signal of CSL in membrane incubated with 0 µM α-crystallin and 53 µM α-crystallin are shown in Figure 7 (The concentration of POPC was fixed to 9.4 mM). Measurements were performed for deoxygenated samples (100% N2) and samples equilibrated with selected air/nitrogen mixture. All saturation-recovery EPR signals shown in Figure 7 were satisfactorily fit to a single exponential function. As can be seen from residuals (the experimental signal minus the fitting curve) in all cases, the single-exponential fit was excellent.
Stability of a high-concentration monoclonal antibody solution produced by liquid–liquid phase separation
Published in mAbs, 2021
Jack E. Bramham, Stephanie A. Davies, Adrian Podmore, Alexander P. Golovanov
NMR transverse relaxation rates (R2) are coupled to molecular motions and apparent molecular size through rotational correlation time, and so report on apparent intermolecular interactions. The similar R2 spectral profiles (Figure 2b) between the three 10 mg/mL solutions show that protein–protein interactions and colloidal behavior of COE-13 are not perturbed irreversibly by LLPS. Conversely, R2 was markedly faster in the intact dense fraction, such that COE-13 relaxation rates were essentially unmeasurable in this fraction. Along with the significantly reduced signal, this suggests significant attractive protein–protein interactions and the occurrence of protein self-association and high viscosity in the highly concentrated dense fraction. On the other hand, the NMR observations indicate that unperturbed COE-13 is recoverable from the lean fraction and after dilution of the dense fraction, suggesting that the self-association observed in the dense fraction is fully reversible.