Fmoc-Lys(Boc)-OH-[13]C6,[15]N2 | 850080-89-6

• 物质功能分类: 分析化学 - 标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Lys(Boc)-OH-[13]C6,[15]N2
• 英文别名: [¹³C₆,¹⁵N₂]-Fmoc-L-lysine(Boc)-OH；Nα-[U-13C6,15N2]Fmoc-Nε-Boc-lysine；Fmoc-Lys(Boc)-OH-13C6,15N2；(2S)-2-(9H-fluoren-9-ylmethoxycarbonyl(15N)amino)-6-[(2-methylpropan-2-yl)oxycarbonyl(15N)amino](1,2,3,4,5,6-13C6)hexanoic acid
• CAS: 850080-89-6
• 化学式: C₂₆H₃₂N₂O₆
• 分子量: 476.47
• InChiKey: UMRUUWFGLGNQLI-OYSAUITLSA-N

物化性质

• 熔点：
  130-135 °C(lit.)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

制备方法与用途

简介

Fmoc-L-Lys (Boc)-OH-13C6,15N2 是一种带有 15N 和 13C 标记的苯达唑化合物，具有三个同位素标记。

用途

[U-13C6,U-15N2]-芴甲氧羰基-赖氨酸-叔丁氧羰基中的稳定重同位素（包括氢、碳和其他元素）被纳入药物分子中，主要用于药物开发过程中的定量示踪剂。氘化因可能影响药物的药代动力学和代谢特征而备受关注。

反应信息

• 作为反应物：
  描述：

  Fmoc-Lys(Boc)-OH-[13]C6,[15]N2 在 三氟乙酸 作用下， 反应 2.0h， 生成 Nα-[U-13C6,15N2]Fmoc-lysine
  参考文献：
  名称：

  Lipid Peroxidation Generates Body Odor Component trans-2-Nonenal Covalently Bound to Protein in Vivo

  摘要：

  trans-2-Nonenal is an unsaturated aldehyde with an unpleasant greasy and grassy odor endogenously generated during the peroxidation of polyunsaturated fatty acids. 2-Nonenal covalently modified human serum albumin through a reaction in which the aldehyde preferentially reacted with the lysine residues. Modified proteins were immunogenic, and a specific monoclonal antibody (mAb) 27Q4 that cross-reacted with the protein covalently modified with 2-nonenal was raised from mouse. To verify the presence of the protein-bound 2-nonenal in vivo, the mAb 27Q4 against the 2-nonenal-modified keyhole limpet hemocyanin was raised. It was found that a novel 2-nonenal-lysine adduct, cis- and trans-N-epsilon-3-[(hept-1-enyl)-4-hexyl-pyridinium]lysine (HHP-lysine), constitutes an epitope of the antibody. The immunoreactive materials with mAb 27Q4 were detected in the kidney of rats exposed to ferric nitrilotriacetate, an iron chelate that induces free radical-mediated oxidative tissue damage. Using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry, we also established a highly sensitive method for detection of the cis- and trans-HHP-lysine and confirmed that the 2-nonenal-lysine adducts were indeed formed during the lipid peroxidation-mediated modification of protein in vitro and in vivo. Furthermore, we examined the involvement of the scavenger receptor lectin-like oxidized low density lipoprotein receptor-1 in the recognition of 2-nonenal-modified proteins and established that the receptor recognized the HHP-lysine adducts as a ligand.

  DOI：

  10.1074/jbc.m109.068023

文献信息

• Selective Deletion of the Internal Lysine Residue from the Peptide Sequence by Collisional Activation
  作者：Shibdas Banerjee、Shyamalava Mazumdar

  DOI：10.1007/s13361-012-0456-1

  日期：2012.11.1

  The gas-phase peptide ion fragmentation chemistry is always the center of attraction in proteomics to analyze the amino acid sequence of peptides and proteins. In this work, we describe the formation of an anomalous fragment ion, which corresponds to the selective deletion of the internal lysine residue from a series of lysine containing peptides upon collisional activation in the ion trap. We detected several water-loss fragment ions and the maximum number of water molecules lost from a particular fragment ion was equal to the number of lysine residues in that fragment. As a consequence of this water-loss phenomenon, internal lysine residues were found to be deleted from the peptide ion. The N,N-dimethylation of all the amine functional groups of the peptide stopped the internal lysine deletion reaction, but selective N-terminal α-amino acetylation had no effect on this process indicating involvement of the side chains of the lysine residues. The detailed mechanism of the lysine deletion was investigated by multistage CID of the modified and unmodified peptides, by isotope labeling and by energy resolved CID studies. The results suggest that the lysine deletion might occur through a unimolecular multistep mechanism involving a seven-membered cyclic imine intermediate formed by the loss of water from a lysine residue in the protonated peptide. This intermediate subsequently undergoes degradation reaction to deplete the interior imine ring from the peptide backbone leading to the deletion of an internal lysine residue.

  气相肽离子碎裂化学一直是蛋白质组学中分析肽和蛋白质氨基酸序列的焦点。在本工作中，我们描述了异常碎片离子的形成，这些碎片离子对应于一系列含有赖氨酸的肽在离子阱中碰撞激活后选择性地删除内部赖氨酸残基。我们检测到了几个失水碎片离子，并且从一个特定碎片离子损失的最大水分子数等于该碎片中赖氨酸残基的数量。因此，内部赖氨酸残基被发现从肽离子中删除。所有胺官能团的N,N-二甲基化阻止了内部赖氨酸删除反应，但选择性N-末端α-氨基乙酰化对这一过程没有影响，表明涉及到赖氨酸残基的侧链。通过修饰和未修饰肽的多级CID、同位素标记和能量解析CID研究，详细探讨了赖氨酸删除的机制。结果表明，赖氨酸删除可能通过涉及由肽质子化中赖氨酸残基失水形成的七元环状亚胺中间体的单分子多步机制发生。随后，该中间体经历降解反应，从肽主链中耗尽内部亚胺环，导致删除内部赖氨酸残基。
• Lipid Peroxidation Generates Body Odor Component trans-2-Nonenal Covalently Bound to Protein in Vivo
  作者：Kousuke Ishino、Chika Wakita、Takahiro Shibata、Shinya Toyokuni、Sachiko Machida、Shun Matsuda、Tomonari Matsuda、Koji Uchida

  DOI：10.1074/jbc.m109.068023

  日期：2010.5

  trans-2-Nonenal is an unsaturated aldehyde with an unpleasant greasy and grassy odor endogenously generated during the peroxidation of polyunsaturated fatty acids. 2-Nonenal covalently modified human serum albumin through a reaction in which the aldehyde preferentially reacted with the lysine residues. Modified proteins were immunogenic, and a specific monoclonal antibody (mAb) 27Q4 that cross-reacted with the protein covalently modified with 2-nonenal was raised from mouse. To verify the presence of the protein-bound 2-nonenal in vivo, the mAb 27Q4 against the 2-nonenal-modified keyhole limpet hemocyanin was raised. It was found that a novel 2-nonenal-lysine adduct, cis- and trans-N-epsilon-3-[(hept-1-enyl)-4-hexyl-pyridinium]lysine (HHP-lysine), constitutes an epitope of the antibody. The immunoreactive materials with mAb 27Q4 were detected in the kidney of rats exposed to ferric nitrilotriacetate, an iron chelate that induces free radical-mediated oxidative tissue damage. Using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry, we also established a highly sensitive method for detection of the cis- and trans-HHP-lysine and confirmed that the 2-nonenal-lysine adducts were indeed formed during the lipid peroxidation-mediated modification of protein in vitro and in vivo. Furthermore, we examined the involvement of the scavenger receptor lectin-like oxidized low density lipoprotein receptor-1 in the recognition of 2-nonenal-modified proteins and established that the receptor recognized the HHP-lysine adducts as a ligand.