N6-[(benzylamino)carbonothioyl]lysine | 1211456-34-6

• 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: N6-[(benzylamino)carbonothioyl]lysine
• 英文别名: (2S)-2-amino-6-(benzylcarbamothioylamino)hexanoic acid
• CAS: 1211456-34-6
• 化学式: C₁₄H₂₁N₃O₂S
• 分子量: 295.406
• InChiKey: SUDSAMPFROMSLM-LBPRGKRZSA-N

物化性质

• 沸点：
  490.3±55.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于酸水溶液（轻微），DMSO（轻微，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异硫氰酸苯甲酯 、 N-alpha-叔丁氧羰基-L-赖氨酸 在 碳酸氢钠 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以71.3%的产率得到N6-[(benzylamino)carbonothioyl]lysine
  参考文献：
  名称：

  New Biomarkers for Monitoring the Levels of Isothiocyanates in Humans

  摘要：

  Isothiocyanates (ITCs) found in cruciferous vegetables have demonstrated cancer preventive activity in animals, and increased dietary intake of ITCs has been shown to be associated with a reduced cancer risk in humans. ITCs exert their cancer chemopreventive action by multiple mechanisms, for example, by modulating the activities of phase 1 and phase II drug metabolism enzymes, by inhibiting the cell cycle and histone deacetylase, and by causing apoptotic cell death. In cells, protein adducts account for most of total cellular ITC uptake at 4 h after treatment. The time course of this protein binding correlates well with the inhibition of proliferation and the induction of apoptosis. Animal studies have shown that glutathione conjugates are the major products of ITCs. The major urinary excretion products of ITCs in human are N-acetyl cysteine conjugates. Urinary metabolites might provide the exposure history of the last 24 h, if the urine of the full next day is collected. However, this is not feasible in large epidemiological studies. Furthermore, the mercapturic acids of ITC are not stable. Therefore, stable biomarkers are needed that reflect a larger time span of the ITC exposure history. We developed a method to determine stable (not cysteine adducts) reaction products of ITCs with albumin and hemoglobin in humans and mice. We reacted albumin with the ITCs: benzyl isothiocyanate (BITC), phenylethyl isothiocyanate (PEITC), sulforaphane (SFN), and ally! isothiocyanate (AITC). After enzymatic digestion, we found one major product with lysine using LC-MS/MS. The identity of the adducts was confirmed by comparing the analyses with synthetic standards: N-6-[(benzylamino)carbonothioyl]lysine (BITC-Lys), N-6-{[(2-phenylethypamino]carbonothioyl}lysine (PEITC-Lys), N-6-({[3-(methylsulfinyl)propyl]amino}carbonothioyl)lysine (SFN-Lys), and N-6-[(allylamino]carbonothioyl]lysine (AITC-Lys). The adduct levels were quantified by isotope dilution mass spectrometry using the corresponding new ITC-[(C6N2)-C-13-N-15]lysines as internal standards. The applicability of the method was tested for biological samples obtained from different experiments. In humans consuming garden cress, watercress, and broccoli and/or in mice exposed chronically to N-acetyl-S-{[(2-phenylethyl)amino]carbonothioyl}-L-cysteine, albumin and hemoglobin adducts were found. BITC-Lys, PEITC-Lys, and SFN-Lys released after enzymatic digestion of the proteins were quantified with LC-MS/MS. This new method will enable quantification of ITC adducts in blood proteins from large prospective studies about diet and cancer. Protein adducts are involved in the chemopreventive effects of ITCs. Therefore, blood protein adducts are a potential surrogate marker for the effects of ITCs at the cellular level. This new technique will improve the assessment of ITC exposure and the power of studies on the relationship between ITC intake and cancer.

  DOI：

  10.1021/tx900393t

文献信息

• New Biomarkers for Monitoring the Levels of Isothiocyanates in Humans
  作者：Anoop Kumar、Gabriele Sabbioni

  DOI：10.1021/tx900393t

  日期：2010.4.19

  Isothiocyanates (ITCs) found in cruciferous vegetables have demonstrated cancer preventive activity in animals, and increased dietary intake of ITCs has been shown to be associated with a reduced cancer risk in humans. ITCs exert their cancer chemopreventive action by multiple mechanisms, for example, by modulating the activities of phase 1 and phase II drug metabolism enzymes, by inhibiting the cell cycle and histone deacetylase, and by causing apoptotic cell death. In cells, protein adducts account for most of total cellular ITC uptake at 4 h after treatment. The time course of this protein binding correlates well with the inhibition of proliferation and the induction of apoptosis. Animal studies have shown that glutathione conjugates are the major products of ITCs. The major urinary excretion products of ITCs in human are N-acetyl cysteine conjugates. Urinary metabolites might provide the exposure history of the last 24 h, if the urine of the full next day is collected. However, this is not feasible in large epidemiological studies. Furthermore, the mercapturic acids of ITC are not stable. Therefore, stable biomarkers are needed that reflect a larger time span of the ITC exposure history. We developed a method to determine stable (not cysteine adducts) reaction products of ITCs with albumin and hemoglobin in humans and mice. We reacted albumin with the ITCs: benzyl isothiocyanate (BITC), phenylethyl isothiocyanate (PEITC), sulforaphane (SFN), and ally! isothiocyanate (AITC). After enzymatic digestion, we found one major product with lysine using LC-MS/MS. The identity of the adducts was confirmed by comparing the analyses with synthetic standards: N-6-[(benzylamino)carbonothioyl]lysine (BITC-Lys), N-6-[(2-phenylethypamino]carbonothioyl}lysine (PEITC-Lys), N-6-([3-(methylsulfinyl)propyl]amino}carbonothioyl)lysine (SFN-Lys), and N-6-[(allylamino]carbonothioyl]lysine (AITC-Lys). The adduct levels were quantified by isotope dilution mass spectrometry using the corresponding new ITC-[(C6N2)-C-13-N-15]lysines as internal standards. The applicability of the method was tested for biological samples obtained from different experiments. In humans consuming garden cress, watercress, and broccoli and/or in mice exposed chronically to N-acetyl-S-[(2-phenylethyl)amino]carbonothioyl}-L-cysteine, albumin and hemoglobin adducts were found. BITC-Lys, PEITC-Lys, and SFN-Lys released after enzymatic digestion of the proteins were quantified with LC-MS/MS. This new method will enable quantification of ITC adducts in blood proteins from large prospective studies about diet and cancer. Protein adducts are involved in the chemopreventive effects of ITCs. Therefore, blood protein adducts are a potential surrogate marker for the effects of ITCs at the cellular level. This new technique will improve the assessment of ITC exposure and the power of studies on the relationship between ITC intake and cancer.