DRVY(NO2)IHPF

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: DRVY(NO2)IHPF
• 英文别名: NO2-Ang II；DRVnYIHPF；H-Asp-Arg-Val-Tyr(3-NO2)-Ile-His-Pro-Phe-OH；(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxy-3-nitrophenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
• 化学式: C₅₀H₇₀N₁₄O₁₄
• 分子量: 1091.19
• InChiKey: GJNQQQUIJLVSCN-UGRZSYFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  78
• 可旋转键数：
  29
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  455
• 氢给体数：
  13
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  血管紧张素II 在 四硝基甲烷 作用下， 反应 1.0h， 生成 DRVY(NO2)IHPF
  参考文献：
  名称：

  Characterization of Tyrosine Nitration and Cysteine Nitrosylation Modifications by Metastable Atom-Activation Dissociation Mass Spectrometry

  摘要：

  利用碰撞诱导解离（CID）和陨落原子激活解离质谱（MAD-MS）研究了硝化肽和S-亚硝基化肽的碎裂行为。将修饰肽和未修饰肽的各种电荷状态（如 1+、2+、3+、2-）暴露在高动能氦（He）惰性原子束中，会导致广泛的骨架破碎，并显著保留翻译后修饰（PTMs）。虽然硝基酪氨酸分子的高电子亲和力可以淬灭电子捕获解离（ECD）和电子转移解离（ETD）中的自由基化学反应和碎片，但 MAD 确实会在修饰附近产生大量的骨架裂解。亚硝基化半胱氨酸修饰的碎片离子通常比亚硝基化酪氨酸修饰的中性损失更多，这是因为亚硝基化半胱氨酸残基的性质极其易变。然而，与 CID 相比，MAD 产生的片段离子增加了 66% 至 86%，保留了易变的 -NO 修饰。MAD 还能区分修饰肽中的 I/L 残基。MAD 即使在强自由基捕获器存在的情况下也能诱导自由基离子化学反应，因此与 ECD、ETD 和 CID 相比，它在测定硝化肽和 S-亚硝基化肽等 PTMs 方面具有独特的优势。

  DOI：

  10.1007/s13361-010-0041-4

文献信息

• Investigation of tyrosine nitration in proteins by mass spectrometry
  作者：Ann-Sofi Petersson、Hanno Steen、D�rio E. Kalume、Kenneth Caidahl、Peter Roepstorff

  DOI：10.1002/jms.161

  日期：2001.6

  In vivo nitration of tyrosine residues is a post-translational modification mediated by peroxynitrite that may be involved in a number of diseases. The aim of this study was to evaluate possibilities for site-specific detection of tyrosine nitration by mass spectrometry. Angiotensin II and bovine serum albumin (BSA) nitrated with tetranitromethane (TNM) were used as model compounds. Three strategies were investigated: (i) analysis of single peptides and protein digests by matrix-assisted laser desorption/ionization (MALDI) peptide mass mapping, (ii) peptide mass mapping by electrospray ionization (ESI) mass spectrometry and (iii) screening for nitration by selective detection of the immonium ion of nitrotyrosine by precursor ion scanning with subsequent sequencing of the modified peptides. The MALDI time-of-flight mass spectrum of nitrated angiotensin II showed an unexpected prompt fragmentation involving the nitro group, in contrast to ESI-MS, where no fragmentation of nitrated angiotensin II was observed. The ESI mass spectra showed that mono- and dinitrated angiotensin II were obtained after treatment with TNM. ESI-MS/MS revealed that the mononitrated angiotensin II was nitrated on the side-chain of tyrosine. The dinitrated angiotensin II contained two nitro groups on the tyrosine residue. Nitration of BSA was confirmed by Western blotting with an antibody against nitrotyrosine and the sites for nitration were investigated by peptide mass mapping after in-gel digestion. Direct mass mapping by ESI revealed that two peptides were nitrated. Precursor ion scanning for the immonium ion for nitrotyrosine revealed two additional partially nitrated peptides. Based on the studies with the two model compounds, we suggest that the investigation of in vivo nitration of tyrosine and identification of nitrated peptides might be performed by precursor ion scanning for the specific immonium ion at m/z 181.06 combined with ESI-MS/MS for identification of the specific nitration sites. Copyright © 2001 John Wiley & Sons, Ltd.

  酪氨酸残基的体内硝化作用是一种由过氧化亚硝酸盐介导的翻译后修饰，可能与多种疾病有关。本研究的目的是评估通过质谱法对酪氨酸硝化作用进行定点检测的可能性。以四硝基甲烷（TNM）硝化的血管紧张素II和牛血清白蛋白（BSA）作为模型化合物。研究了三种策略：（1）通过基质辅助激光解吸/电离（MALDI）肽图分析单肽和蛋白质消化产物；（2）通过电喷雾电离（ESI）质谱分析肽图；（3）通过前体离子扫描选择性检测硝基酪氨酸的鎓离子，并随后对修饰肽进行测序，以筛选硝化作用。硝化血管紧张素II的MALDI飞行时间质谱显示，硝基基团出现了意外的快速断裂，这与ESI-MS不同，在ESI-MS中未观察到硝化血管紧张素II的断裂。ESI质谱显示，经TNM处理后，获得了单硝化和二硝化的血管紧张素II。ESI-MS/MS显示，单硝化的血管紧张素II在酪氨酸侧链上被硝化。二硝化的血管紧张素II在酪氨酸残基上含有两个硝基基团。通过硝基酪氨酸抗体进行蛋白质印迹实验，证实了BSA的硝化作用，
• Characterization of Tyrosine Nitration and Cysteine Nitrosylation Modifications by Metastable Atom-Activation Dissociation Mass Spectrometry
  作者：Shannon L. Cook、Glen P. Jackson

  DOI：10.1007/s13361-010-0041-4

  日期：2011.2.1

  The fragmentation behavior of nitrated and S-nitrosylated peptides were studied using collision induced dissociation (CID) and metastable atom-activated dissociation mass spectrometry (MAD-MS). Various charge states, such as 1+, 2+, 3+, 2–, of modified and unmodified peptides were exposed to a beam of high kinetic energy helium (He) metastable atoms resulting in extensive backbone fragmentation with significant retention of the post-translation modifications (PTMs). Whereas the high electron affinity of the nitrotyrosine moiety quenches radical chemistry and fragmentation in electron capture dissociation (ECD) and electron transfer dissociation (ETD), MAD does produce numerous backbone cleavages in the vicinity of the modification. Fragment ions of nitrosylated cysteine modifications typically exhibit more abundant neutral losses than nitrated tyrosine modifications because of the extremely labile nature of the nitrosylated cysteine residues. However, compared with CID, MAD produced between 66% and 86% more fragment ions, which preserved the labile –NO modification. MAD was also able to differentiate I/L residues in the modified peptides. MAD is able to induce radical ion chemistry even in the presence of strong radical traps and therefore offers unique advantages to ECD, ETD, and CID for determination of PTMs such as nitrated and S-nitrosylated peptides.

  利用碰撞诱导解离（CID）和陨落原子激活解离质谱（MAD-MS）研究了硝化肽和S-亚硝基化肽的碎裂行为。将修饰肽和未修饰肽的各种电荷状态（如 1+、2+、3+、2-）暴露在高动能氦（He）惰性原子束中，会导致广泛的骨架破碎，并显著保留翻译后修饰（PTMs）。虽然硝基酪氨酸分子的高电子亲和力可以淬灭电子捕获解离（ECD）和电子转移解离（ETD）中的自由基化学反应和碎片，但 MAD 确实会在修饰附近产生大量的骨架裂解。亚硝基化半胱氨酸修饰的碎片离子通常比亚硝基化酪氨酸修饰的中性损失更多，这是因为亚硝基化半胱氨酸残基的性质极其易变。然而，与 CID 相比，MAD 产生的片段离子增加了 66% 至 86%，保留了易变的 -NO 修饰。MAD 还能区分修饰肽中的 I/L 残基。MAD 即使在强自由基捕获器存在的情况下也能诱导自由基离子化学反应，因此与 ECD、ETD 和 CID 相比，它在测定硝化肽和 S-亚硝基化肽等 PTMs 方面具有独特的优势。