Imidazolium Compounds as Internal Exchange Reporters for Hydrogen/Deuterium Exchange by Mass Spectrometry.
Imidazolium Compounds as Internal Exchange Reporters for Hydrogen/Deuterium Exchange by Mass Spectrometry.
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DOI：
10.1021/acs.analchem.0c01328
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发表时间：
2020-07-21
影响因子：
7.4
通讯作者：
Guttman M
中科院分区：
文献类型：
--
作者：
Murphree TA;Vorauer C;Brzoska M;Guttman M
氢氘交换质谱（HDX-MS）是一种功能强大的蛋白质结构分析工具，非常适合生物治疗开发和表征。因为HDX强烈依赖于溶液条件；即使温度或pH值的微小变化也会对交换动力学产生显著影响，这可能表现为运行间的显著可变性和降低再现性。最近，人们开始关注内部交易所报告者（IERs）的发展，这种报告者可以直接监测交易所反应条件的变化。然而，目前可用的小肽ier只能在非常窄的时间窗口内采样，并且在其HDX动力学中表现出复杂的溶液依赖性。在这里，我们证明使用咪唑碳酸作为HDX-MS的优越的IERs。这些化合物在各种反应条件下表现出可预测的交换行为，高度稳定，并且可以很容易地进行修改以在很宽的时间窗口内进行交换。使用这些化合物作为溶液基HDX-MS的IERs，可以通过允许更稳健的经验交换校正从而提高再现性，从而大大扩展该技术的实用性。
Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful tool for protein structure analysis that is well suited for biotherapeutic development and characterization. Because HDX is strongly dependent on solution conditions; even small variations in temperature or pH can have a pronounced effect on the exchange kinetics that can manifest in significant run-to-run variability and compromise reproducibility. Recent attention has been given to the development of internal exchange reporters (IERs), which directly monitor changes to exchange reaction conditions. However, the currently available small peptide IERs are only capable of sampling a very narrow temporal window and are understood to exhibit complex solution dependence in their HDX kinetics. Here we demonstrate the use of imidazolium carbon acids as superior IERs for HDX-MS. These compounds exhibit predictable exchange behavior under a wide variety of reaction conditions, are highly stable, and can be readily modified to exchange over a broad temporal window. The use of these compounds as IERs for solution based HDX-MS could considerably extend the utility of the technique by allowing for more robust empirical exchange correction thereby improving reproducibility.
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影响因子：
2.9
作者：
Hayashi, Naoka;Kuyama, Hiroki;Nakajima, Chihiro;Kawahara, Kazuki;Miyagi, Masaru;Nishimura, Osamu;Matsuo, Hisayuki;Nakazawa, Takashi
通讯作者：
Nakazawa, Takashi
影响因子：
3.6
作者：
Gottlieb, HE;Kotlyar, V;Nudelman, A
通讯作者：
Nudelman, A
影响因子：
7.4
作者：
Porras, SP;Sarmini, K;Kenndler, E
通讯作者：
Kenndler, E
影响因子：
48
作者：
Masson, Glenn R.;Burke, John E.;Rand, Kasper D.
通讯作者：
Rand, Kasper D.
DOI：
10.1016/s1044-0305(02)00384-7
发表时间：
2002-06-01
影响因子：
3.2
作者：
Schwartz, JC;Senko, MW;Syka, JEP
通讯作者：
Syka, JEP