Molecular Recognition of R- and T-States of Human Adult Hemoglobin by a Paramagnetic Gd(III) Complex by Means of the Measurement of Solvent Water Proton Relaxation Rate

1995 ◽  
Vol 117 (36) ◽  
pp. 9365-9366 ◽  
Author(s):  
Silvio Aime ◽  
Paolo Ascenzi ◽  
Elena Comoglio ◽  
Mauro Fasano ◽  
Silvia Paoletti
Keyword(s):  
Molecular Recognition ◽  
Relaxation Rate ◽  
Water Proton ◽  
Proton Relaxation ◽  
Solvent Water ◽  
Human Adult ◽  
Adult Hemoglobin

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

2021 ◽  
pp. 193229682110238
Author(s):  
Marc B. Taraban ◽  
Yilin Wang ◽  
Katharine T. Briggs ◽  
Yihua Bruce Yu
Keyword(s):  
Quality Control ◽  
Relaxation Rate ◽  
Drug Product ◽  
Proton Nmr ◽  
Water Proton ◽  
Proton Relaxation ◽  
Content Uniformity ◽  
Biologic Drugs ◽  
Insulin Solution ◽  
Insulin Pens

Background: There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Methods: Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Results: Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Conclusions: Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.

Water Proton Relaxation Rate Enhancements and Association Constants for Mn(II) to Serum Proteins Determined by NMR T1 Measurements

2005 ◽  
Vol 60 (9-10) ◽  
pp. 807-812 ◽  
Author(s):  
Hatice Budak
Keyword(s):  
Serum Albumin ◽  
Human Serum ◽  
Relaxation Rate ◽  
Association Constant ◽  
Serum Proteins ◽  
Association Constants ◽  
Water Proton ◽  
Proton Relaxation ◽  
Rate Enhancement ◽  
Human Serum Proteins

Abstract The water proton relaxation rate enhancement of Mn(II) bound to bovine serum albumin (BSA) and the association constant for manganese to BSA have already been determined, but such determinations have not been done for human serum albumin (HSA) and other human serum proteins and also for human serum. In this work, NMR T1 values in aqueous solutions of serum proteins and serum were measured versus increasing concentration of Mn(II). Proton relaxation rate enhancements (ε*) caused by different manganese concentrations were determined for each solution and 1/ε* was fitted against concentrations of Mn(II). Proton relaxation rate enhancements (εb) of Mn(II) bound to albumin, γ-globulin, (α+β)- globulins and serum were found to be 13.69, 3.09, 8.62, and 10.87, respectively. Free and bound manganese fractions, resulted from each addition of Mn(II) to the sample, were determined by using corresponding (ε*) and the εb values. Association constants for Mn(II) to HSA and γ-globulin were calculated as 1.84 x 104 ᴍ-1 and 2.35 x 104 ᴍ-1, respectively. Present data suggest that the proton relaxation rate enhancement of Mn(II) in serum is caused by Mn(II) bound to various serum constituents. Data also suggest that association constants for Mn(II) to γ-globulin are nearly the same as that to HSA.

Nature of lysozyme–water interactions by proton NMR

1991 ◽  
Vol 69 (5-6) ◽  
pp. 341-345 ◽  
Author(s):  
S. Prosser ◽  
H. Peemoeller
Keyword(s):  
Relaxation Rate ◽  
Proton Nmr ◽  
Lattice Relaxation ◽  
Proton Spin ◽  
Spin Lattice Relaxation ◽  
Water Proton ◽  
Proton Relaxation ◽  
Spin Lattice ◽  
Proton Coupling ◽  
Relaxation Measurements

Proton spin-lattice relaxation measurements were performed in 10 mM lysozyme solution as a function of temperature and degree of substitution of solvent H2O with D2O. The results show that in the temperature range from 274 to 323 K, the intermolecular lysozyme proton water proton coupling contributes appreciably to the observed water proton relaxation rate. In this system exchange between water protons and labile protein protons does not dominate the behaviour with temperature of the water–lysozyme intermolecular contribution to the spin-lattice relaxation.Key words: NMR, lysozyme, relaxation-contributions.

Quantitative Determination of Methemoglobin by Measuring the Solvent-Water Proton-Nuclear Magnetic Resonance Relaxation Rate

1992 ◽  
Vol 38 (12) ◽  
pp. 2401-2404 ◽  
Author(s):  
S Aime ◽  
W Dastrú ◽  
M Fasano ◽  
A Arnelli ◽  
M Castagnola ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Quantitative Determination ◽  
Relaxation Rate ◽  
Proton Nuclear Magnetic Resonance ◽  
Water Proton ◽  
Simple Relationship ◽  
Solvent Water ◽  
Nuclear Magnetic

Abstract We report a new method for the quantitative determination of human methemoglobin (metHb) based on the measurement of the solvent-water proton-nuclear magnetic resonance (NMR) relaxation rate R1 [normalized to 1 mmol/L hemoglobin (Hb) concentration]. MetHb (%) is estimated from the linear dependence of R1 on the metHb concentration, taking into account the simple relationship [MetHb] = [(R1 - R1HbO2)/(R1metHb - R1HbO2)].100, where R1HbO2 and R1metHb are values for the solvent-water relaxation rate of standard 1.0 mmol/L solutions of the oxygenated derivative of human hemoglobin (HbO2) and of metHb, respectively. The minimum metHb that may be determined from the analysis of the experimental data is 0.5 +/- 0.4%.

scholarly journals Revisiting paramagnetic relaxation enhancements in slowly rotating systems: how long is the long range?

2021 ◽  
Vol 2 (1) ◽  
pp. 25-31
Author(s):  
Giovanni Bellomo ◽  
Enrico Ravera ◽  
Vito Calderone ◽  
Mauro Botta ◽  
Marco Fragai ◽  
...  
Keyword(s):  
Relaxation Rate ◽  
Chemical Exchange ◽  
Protein Structure Determination ◽  
Bulk Water ◽  
Paramagnetic Relaxation ◽  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Rotating Systems ◽  
Order Of Magnitude

Abstract. Cross-relaxation terms in paramagnetic systems that reorient rigidly with slow tumbling times can increase the effective longitudinal relaxation rates of protons of more than 1 order of magnitude. This is evaluated by simulating the time evolution of the nuclear magnetization using a complete relaxation rate-matrix approach. The calculations show that the Solomon dependence of the paramagnetic relaxation rates on the metal–proton distance (as r−6) can be incorrect for protons farther than 15 Å from the metal and thus can cause sizable errors in R1-derived distance restraints used, for instance, for protein structure determination. Furthermore, the chemical exchange of these protons with bulk water protons can enhance the relaxation rate of the solvent protons by far more than expected from the paramagnetic Solomon equation. Therefore, it may contribute significantly to the water proton relaxation rates measured at magnetic resonance imaging (MRI) magnetic fields in the presence of slow-rotating nanoparticles containing paramagnetic ions and a large number of exchangeable surface protons.

scholarly journals The use of gadolinium as a probe in the Fc region of a homogeneous anti-(type-III pneumococcal polysaccharide) antibody

1977 ◽  
Vol 161 (2) ◽  
pp. 205-211 ◽  
Author(s):  
K J Willan ◽  
K H Wallace ◽  
J C Jaton ◽  
R A Dwek
Keyword(s):  
Water Proton ◽  
Proton Relaxation ◽  
Relaxation Rates ◽  
Fab Fragment ◽  
Fc Fragment ◽  
Type Iii ◽  
Solvent Water ◽  
Specificity Of Binding ◽  
Polysaccharide Antibody ◽  
Antigen Antibody

The binding of gadolinium [Gd(III)] to a homogeneous rabbit anti-(type-III pneumococcal polysaccharide) IgG (immunoglobulin G) and its Fab (N-terminal half of heavy and light chain) and Fc (C-terminal half of heavy-chain dimer) fragments was demonstrated by measurements of solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 the binding of Gd(III) to the Fc fragment is much tighter (KD approx. 5 micronM) than binding to the Fab fragment (KD approx. 250 micronM). The binding of Gd(III) to the whole IgG molecule (KD approx. 4 micronM) is very similar to that for the Fc fragment alone. This specificity of binding to the Fc region allows the use of Gd(III) as a probe of the Fc conformation. The environment of the Gd(III) in the Fc region of whole IgG is not affected by the presence of octasaccharide derived by hydrolysis of type-III pneumococcal polysaccharide, but the corresponding 28-unit saccharide does cause detectable changes. The addition of 16-unit saccharide to anti-(SIII polysaccharide) IgG in the presence of Gd(III) does not change the solvent water proton relaxation rate, although aggregation does occur. The effects of the 28-unit saccharide may be explained therefore by a change in the tumbling time of the IgG. From a study of the effect of various antigen/antibody ratios, it is concluded that the 28-unit-saccharide-induced changes in the Gd(III) environment in the Fc region are caused by the specific geometrical structure of the antigen-antibody complexes formed, and not simply by occupancy of the combining sites on the antibody.

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