Proton exchange rates from amino acid side chains— implications for image contrast

Abstract

The proton exchange rates between water and the hydroxyl protons of threonine, serine, tyrosine, the amino protons of lysine, and the guanidinium protons of arginine were measured in the pH range 0.5 to 8.5 and for the temperatures 4 degrees C, 10 degrees C, 20 degrees C, 30 degrees C, and 36 degrees C. The intrinsic exchange rates of the hydroxyl and amino protons at pH 7.0 degrees C and 36 degrees C were found to be in the range 700 to about 10,000 s-1. In addition, the exchange catalysis by phosphate, carbonate, carboxyl-, and amino-groups was investigated. The presence of these exchange catalysts at physiological concentrations increased the proton exchange rates from hydroxyl and amino groups several fold. The proton exchange rates are sufficiently fast that the total magnetization transfer between biomolecules and free bulk water is not rate limited by the proton exchange rate, but by the intramolecular cross-relaxation rates between the exchangeable and nonexchangeable protons of the biomolecules. Since the cross-relaxation rates between surface hydration water molecules and biomolecules are usually vanishingly small because of too rapid exchange with the free bulk water, it is proposed that the contrast in MR images is a fingerprint of the number of the exchangeable protons from OH and NH groups of the tissue, as far as the contrast depends on the magnetization transfer between biomolecules and water.

Differential Epitope Mapping by STD NMR Spectroscopy To Reveal the Nature of Protein–Ligand Contacts

“…Here again, the DEEP‐STD NMR results were in line with the crystal structure (Figure 3 c), where the ligand protons H3a, H3e, H9, and H9′ point towards a highly polar patch in the Rg NanH‐GH33 binding pocket (R257, R276, R575, and R637). This is in excellent agreement with the known slow exchanging behavior of η protons of arginine residues in H 2 O 8. Interestingly, the ligand methyl group showed a positive ΔSTD factor (Figure 3 a), which is explained by the presence of a fast exchanging hydroxy group (Y525) close to the methyl groups of V502 (Figure 2 c and Figure S1 in the Supporting Information) 8…”

“…This is in excellent agreement with the known slow exchanging behavior of η protons of arginine residues in H 2 O 8. Interestingly, the ligand methyl group showed a positive ΔSTD factor (Figure 3 a), which is explained by the presence of a fast exchanging hydroxy group (Y525) close to the methyl groups of V502 (Figure 2 c and Figure S1 in the Supporting Information) 8…”

“…In D 2 O, the polar side chains in the binding pocket have their exchangeable protons replaced by 2 H, which is inefficient for transferring saturation 7. In H 2 O, these protons can contribute to an additional transfer of saturation compared to D 2 O 8. This process depends on their exchange rate with bulk water, with slowly exchanging polar protons being expected to produce the largest variations 8.…”

The interaction between magnetization transfer and blood‐oxygen‐level‐dependent effects

“…There are two possible molecular mechanisms responsible for MT between this solid-like matrix and free bulk water (29). The first pathway is through dipolar coupling from protons of the immobilized macromolecular phase to protons of hydration water on the macromolecular surface to protons of the unbound bulk water.…”

MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST)

“…To investigate this possibility, we used chemical exchange saturation transfer (CEST) (21)(22)(23) techniques in which selective radio frequency (RF) irradiation of solute protons is detected through progressive saturation of the water signal as a function of time. Because hydroxyl protons exchange rather quickly with solvent protons [exchange rate, k Ͼ 10 3 per s, (24)], saturated hydroxyl spins on glycogen transfer rapidly to the water protons and thereby reduce the intensity of the water signal. When irradiating for a period of a few seconds, a cumulative saturation of the water signal occurs.…”