Boc-D-Lys(Z)-ONp

• 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: Boc-D-Lys(Z)-ONp
• 英文别名: Boc-D-Lys(Cbz)-OH p-nitrophenyl ester；Boc-D-Lys(Cbz)-OPh(4-NO2)；(4-nitrophenyl) (2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-6-(phenylmethoxycarbonylamino)hexanoate
• 化学式: C₂₅H₃₁N₃O₈
• 分子量: 501.536
• InChiKey: FZHFJIODNQYXRK-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  H-Leu-Arg(Mts)-Tyr-OBzl 、 Boc-D-Lys(Z)-ONp 以79.6%的产率得到Boc-D-Lys(Z)-Leu-Arg(Mts)-Tyr-OBzl
  参考文献：
  名称：

  Amino Acids and Peptides. XXXVII. Synthesis of Stereoisomeric Nonapeptides Corresponding to Sequence 41-49 of Eglin c and Examination of Their Inhibitory Activity against Human Leukocyte Cathepsin G and .ALPHA.-Chymotrypsin.

  摘要：

  一种非apeptide，H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OH，对应于eglin c序列41-49，分别以2.2×10-5和7.2×10-6M的Ki值抑制白细胞组织蛋白酶G和α-胰凝乳蛋白酶，尽管eglin c本身分别以6.0×10-9、5.5×10-9和2.5×10-9M的Ki值抑制白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶。非apeptide的抑制活性在与组织蛋白酶G孵育后下降，这是由于Leu45-Asp46肽键的断裂。因此，Leu45和/或Asp46被替换为D-氨基酸，并对产生的非apeptide的抑制活性进行了检查。它们对组织蛋白酶G和α-胰凝乳蛋白酶的抑制活性远弱于所有L型非apeptide，表明活性位点上的氨基酸，Leu45和Asp46，需要处于L-构型才能发挥强大活性。

  DOI：

  10.1248/cpb.42.1518

文献信息

• Lysine–spermine conjugates: hydrophobic polyamine amides as potent lipopolysaccharide sequestrants
  作者：Mark R. Burns、Stewart J. Wood、Kelly A. Miller、Thuan Nguyen、Jens R. Cromer、Sunil A. David

  DOI：10.1016/j.bmc.2005.01.038

  日期：2005.4

  Lipopolysaccharides (LPS), otherwise termed `endotoxins' are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of `Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states. (c) 2005 Elsevier Ltd. All rights reserved.
• Amino Acids and Peptides. XXXVII. Synthesis of Stereoisomeric Nonapeptides Corresponding to Sequence 41-49 of Eglin c and Examination of Their Inhibitory Activity against Human Leukocyte Cathepsin G and .ALPHA.-Chymotrypsin.
  作者：Ayumi FUJII、Satoshi TSUBOI、Keiichi ASADA、Yoko NAGAMATSU、Junichiro YAMAMOTO、Yoshio OKADA

  DOI：10.1248/cpb.42.1518

  日期：——

  A nonapeptide, H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OH, corresponding to sequence 41-49 of eglin c inhibited leukocyte cathepsin G and α-chymotrypsin with Ki values of 2.2×10-5 and 7.2×10-6M, respectively, although eglin c itself inhibited leukocyte elastase, cathepsin G and α-chymotrypsin with Ki values of 6.0×10-9, 5.5×10-9 and 2.5×10-9M, respectively. The inhibitory activity of the nonapeptide decreased following incubation with cathepsin G due to the cleavage of the Leu45-Asp46 peptide bond. Therefore, Leu45 and/or Asp46 were replaced with D-amino acids and the inhibitory activities of the resultant nonapeptides were examined. Their inhibitory activities against cathepsin G and α-chymotrypsin were much weaker than those of the all-L-type nonapeptide, suggesting that the amino acids at the active site, Leu45 and Asp46 are required to be in the L-configuration for potent activity.

  一种非apeptide，H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OH，对应于eglin c序列41-49，分别以2.2×10-5和7.2×10-6M的Ki值抑制白细胞组织蛋白酶G和α-胰凝乳蛋白酶，尽管eglin c本身分别以6.0×10-9、5.5×10-9和2.5×10-9M的Ki值抑制白细胞弹性蛋白酶、组织蛋白酶G和α-胰凝乳蛋白酶。非apeptide的抑制活性在与组织蛋白酶G孵育后下降，这是由于Leu45-Asp46肽键的断裂。因此，Leu45和/或Asp46被替换为D-氨基酸，并对产生的非apeptide的抑制活性进行了检查。它们对组织蛋白酶G和α-胰凝乳蛋白酶的抑制活性远弱于所有L型非apeptide，表明活性位点上的氨基酸，Leu45和Asp46，需要处于L-构型才能发挥强大活性。