• Mass Spectrometry Letters
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• v.12 no.4
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• pp.131-136
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• 2021

Collision-induced dissociation of peptides involves a series of proton-transfer reactions in the activated peptide. To describe the kinetics of energy-variable dissociation, we considered the heat capacity of the peptide and the Marcus-theory-type proton-transfer rate. The peptide ion was activated to the high internal energy states by collision with a target gas in the collision cell. The mobile proton in the activated peptide then migrated from the most stable site to the amide oxygen and subsequently to the amide nitrogen (N-protonated) of the peptide bond to be broken. The N-protonated intermediate proceeded to the product-like complex that dissociated to products. Previous studies have suggested that the proton-transfer equilibria in the activated peptide affect the dissociation kinetics. To take the extent of collisional activation into account, we assumed a soft-sphere collision model, where the relative collision energy was fully available to the internal excitation of a collision complex. In addition, we employed a Marcus-theory-type rate equation to account for the proton-transfer equilibria. Herein, we present results from the integrated thermochemical approach using a tryptic peptide of ubiquitin.

• Investigative Magnetic Resonance Imaging
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• v.21 no.2
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• pp.65-70
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• 2017

Purpose: To optimize the saturation time and maximizing the pH-weighted difference between the normal and ischemic brain regions, on 3-tesla amide proton transfer (APT) imaging using an in vivo rat model. Materials and Methods: Three male Wistar rats underwent middle cerebral artery occlusion, and were examined in a 3-tesla magnetic resonance imaging (MRI) scanner. APT imaging acquisition was performed with 3-dimensional turbo spin-echo imaging, using a 32-channel head coil and 2-channel parallel radiofrequency transmission. An off-resonance radiofrequency pulse was applied with a Sinc-Gauss pulse at a $B_{1,rms}$ amplitude of $1.2{\mu}T$ using a 2-channel parallel transmission. Saturation times of 3, 4, or 5 s were tested. The APT effect was quantified using the magnetization-transfer-ratio asymmetry at 3.5 ppm with respect to the water resonance (APT-weighted signal), and compared with the normal and ischemic regions. The result was then applied to an acute stroke patient to evaluate feasibility. Results: Visual detection of ischemic regions was achieved with the 3-, 4-, and 5-s protocols. Among the different saturation times at $1.2{\mu}T$ power, 4 s showed the maximum difference between the ischemic and normal regions (-0.95%, P = 0.029). The APTw signal difference for 3 and 5 s was -0.9% and -0.7%, respectively. The 4-s saturation time protocol also successfully depicted the pH-weighted differences in an acute stroke patient. Conclusion: For 3-tesla turbo spin-echo APT imaging, the maximal pH-weighted difference achieved when using the $1.2{\mu}T$ power, was with the 4 s saturation time. This protocol will be helpful to depict pH-weighted difference in stroke patients in clinical settings.

• Bulletin of the Korean Chemical Society
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• v.31 no.8
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• pp.2351-2356
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• 2010

Various dienamide derivatives were synthesized in reasonable yields from benzonitriles having an amide moiety at the ortho-position, via the sequential (i) In-mediated allylation of nitrile moiety to form an imine intermediate, (ii) intramolecular quenching of an acyl group by the imine intermediate, and (iii) a proton transfer to dienamide.

• Korean Journal of Radiology
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• v.22 no.5
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• pp.770-781
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• 2021

Objective: Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. Materials and Methods: Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR_asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. Results: Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR_asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR_asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. Conclusion: CEST MRI potentially allows noninvasive image alterations in the Alzheimer's disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

• Progress in Medical Physics
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• v.28 no.4
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• pp.135-143
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• 2017

Chemical Exchange Saturation Transfer (CEST) imaging is a method to detect solutes based on the chemical exchange of mobile protons with water. The solute protons exchange with three different patterns, which are fast, slow, and intermediate rates. The CEST contrast can be obtained from the exchangeable protons, which are hydroxyl protons, amine protons, and amide protons. The CEST MR imaging is useful to evaluate tumors, strokes, and other diseases. The purpose of this study is to review the mathematical model for CEST imaging and for measurement of the chemical exchange rate, and to measure the chemical exchange rate using a 3T MRI system on several amino acids. We reviewed the mathematical models for the proton exchange. Several physical models are proposed to demonstrate a two-pool, three-pool, and four-pool models. The CEST signals are also evaluated by taking account of the exchange rate, pH and the saturation efficiency. Although researchers have used most commonly in the calculation of CEST asymmetry, a quantitative analysis is also developed by using Lorentzian fitting. The chemical exchange rate was measured in the phantoms made of asparagine (Asn), glutamate (Glu), ${\gamma}-aminobutyric$ acid (GABA), glycine (Gly), and myoinositol (MI). The experiment was performed at a 3T human MRI system with three different acidity conditions (pH 5.6, 6.2, and 7.4) at a concentration of 50 mM. To identify the chemical exchange rate, the "lsqcurvefit" built-in function in MATLAB was used to fit the pseudo-first exchange rate model. The pseudo-first exchange rate of Asn and Gly was increased with decreasing acidity. In the case of GABA, the largest result was observed at pH 6.2. For Glu, the results at pH 5.6 and 6.2 did not show a significant difference, and the results at pH 7.4 were almost zero. For MI, there was no significant difference at pH 5.6 or 7.4, however, the results at pH 6.2 were smaller than at the other pH values. For the experiment at 3T, we were only able to apply 1 s as the maximum saturation duration due to the limitations of the MRI system. The measurement of the chemical exchange rate was limited in a clinical 3T MRI system because of a hardware limitation.