Water proton NMR detection of amide hydrolysis and diglycine dimerization

2018 ◽  
Vol 54 (51) ◽  
pp. 7003-7006 ◽  
Author(s):  
Katharine T. Briggs ◽  
Marc B. Taraban ◽  
Y. Bruce Yu

The transverse relaxation rate of water protonsR2(1H2O) is found to be sensitive to amide hydrolysis and diglycine dimerization.

2015 ◽  
Vol 51 (31) ◽  
pp. 6804-6807 ◽  
Author(s):  
Yue Feng ◽  
Marc B. Taraban ◽  
Yihua Bruce Yu

The transverse relaxation rate of water protons, R2(H2O), can quantify solute association, such as protein aggregation and micelle assembly.


2014 ◽  
Vol 50 (81) ◽  
pp. 12120-12122 ◽  
Author(s):  
Y. Feng ◽  
M. B. Taraban ◽  
Y. B. Yu

It is found that hydrogelation of peptides enhances the transverse relaxation rate R2 of water protons, and the magnitude of such R2 enhancement increases linearly with the shear modulus G of hydrogels.


P. m. r. relaxation times ( T 1 and T 2 ) have been measured as a function of regain and temperature for water sorbed by lyophilized methaemoglobin. The purpose of the work was to gain information regarding the nature and extent of water binding by the protein molecules. The T 1 results are interpreted in terms of an exchange between the sixth ligand position of the Fe (III) and other adsorption sites on the protein. At high temperatures the relaxation rate at a given regain reaches a limiting value which allows the fraction of ferric ions hydrated to be calculated. Above 16% regain all the Fe (III) is hydrated. At 21 and 35% regains a maximum appears in the relaxation rate at about -46 °C indicating a contribution from a more mobile phase which produces a T 1 minimum at that temperature. The T 2 data are consistent with a model in which the main contribution to the transverse relaxation rate comes from a tightly bound fraction of the water with ω 0 Ƭ c ≫1. The temperature dependence of T 2 exhibits three different regions: ( a ) a low temperature region where lg T 2 ∝ T -1 ; ( b ) an intermediate region with a steeper increase of T 2 with temperature; and ( c ) a high temperature where T 2 levels off.


2021 ◽  
pp. 193229682110238
Author(s):  
Marc B. Taraban ◽  
Yilin Wang ◽  
Katharine T. Briggs ◽  
Yihua Bruce Yu

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.


2007 ◽  
Vol 58 (5) ◽  
pp. 1054-1060 ◽  
Author(s):  
Fumiyuki Mitsumori ◽  
Hidehiro Watanabe ◽  
Nobuhiro Takaya ◽  
Michael Garwood

2015 ◽  
Vol 5 ◽  
pp. 1 ◽  
Author(s):  
Grigorios Gotzamanis ◽  
Roman Kocian ◽  
Pinar S. Özbay ◽  
Manuel Redle ◽  
Spyridon Kollias ◽  
...  

Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR) signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen. Materials and Methods: The transverse relaxation rate (R2*) of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO2), and heart pulse rate were monitored during the challenge. R2* maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI) data, acquired at 3.0T. The average values in the segmented white matter (WM) and gray matter (GM) were tested by the analysis of variance (ANOVA), with Bonferroni post-hoc correction. The GM R2*-reactivity to hyperoxia was modeled using the Hill's equation. Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05) decrease of the R2* in GM. Under normoxia the GM-R2* was 17.2 ± 1.1 s-1. At 75% O2 supply, the R2* had reached a saturation level, with 16.4 ± 0.7 s-1 (P = 0.02), without a significant further decrease for 100% O2. The R2*-response of GM correlated positively with CO2 partial pressure (R = 0.69 ± 0.19) and negatively with SaO2 (R = -0.74 ± 0.17). The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055). The Hill's model predicted a maximum R2* response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration. Conclusions: The GM-R2* responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2*-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi174-vi175
Author(s):  
Jingwen Yao ◽  
David Nathanson ◽  
William H Yong ◽  
Noriko Salamon ◽  
Albert Lai ◽  
...  

Abstract 1p/19q co-deleted gliomas are known to have slower growth rates and are more sensitive to chemotherapy and radiotherapy. This may be partially explained by the lower tumor acidosis compared to non-co-deleted gliomas, as extracellular acidosis is one of the driving forces toward tumor invasion and resistance to treatments. Amine CEST-EPI is a fast chemical exchange saturation transfer (CEST) imaging technique sensitive to decreased extracellular pH, transverse relaxation rate, and amino acid concentration. In the current study, we demonstrated that 1p/19q co-deleted gliomas are less acidic than non-co-deleted gliomas, using a combination of pH-sensitive amineCEST-EPI, T2 relaxometry, and 18F-FDOPA (18[F] fluorodopa) amino acid PET. 70 histologically-confirmed glioma patients (World Health Organization WHO grade II, N=35; grade III, N=35) received amine CEST-EPI scans. Among them, 16 patients received 18F-FDOPA PET scan and 45 patients received T2 relaxometry quantification. Mann-Whitney u-test is performed to evaluate the differences. Median MTRasym at 3ppm (magnetization transfer ratio asymmetry at amine proton resonance frequency) within T2 hyperintense lesions was significantly lower in 1p/19q co-deleted gliomas compared to non-co-deleted ones (co-deleted 1.19±0.31%; non-co-deleted 1.66±0.45%; p< 0.0001). The significantly lower MTRasym persists when comparing within grade II (p=0.003), grade III (p=0.031), IDH1 mutated gliomas (p=0.002), and gliomas exhibiting classical oligodendroglial histology (p=0.0007). The ROC analysis shows that the prediction of 1p/19q status using MTRasym has area under the curve (AUC) of 0.80 (sensitivity 75.6%. specificity 72.7%). Median FDOPA and T2 in T2-hyperintense lesions were not different between 1p/19q co-deleted and non-co-deleted tumors (FDOPA p=0.84; T2 p=0.63). Results suggest 1p/19q co-deleted gliomas have notably lower acidity compared with non-co-deleted gliomas, as indicated by lower MTRasym and no differences in amino acid concentration or transverse relaxation rate. Further, data indicate the 1p/19q co-deleted gliomas may have distinct metabolic characteristics and tumor microenvironment that can be measured using pH-sensitive amineCEST-MRI at 3T.


2011 ◽  
Vol 33 (6) ◽  
pp. 1510-1516 ◽  
Author(s):  
Jerry S. Cheung ◽  
Wing-Yan Au ◽  
Shau-Yin Ha ◽  
Daniel Kim ◽  
Jens H. Jensen ◽  
...  

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