BocPhe-Phe-Lys(Z)-CH2Cl | 882173-22-0

• 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: BocPhe-Phe-Lys(Z)-CH2Cl
• 英文别名: Boc-Phe-Phe-Lys(Cbz)-CH2Cl；benzyl N-[(5S)-7-chloro-5-[[(2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-6-oxoheptyl]carbamate
• CAS: 882173-22-0
• 化学式: C₃₈H₄₇ClN₄O₇
• 分子量: 707.267
• InChiKey: FCDVICHYTZFVJZ-CPCREDONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  50
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  BocPhe-Phe-Lys(Z)-CH2Cl 在 苯甲醚 、 三氟乙酸 作用下， 反应 24.0h， 生成 Phe-Phe-Lys-CH2Cl
  参考文献：
  名称：

  Exploring the Sn Binding Pockets in Gingipains by Newly Developed Inhibitors:  Structure-Based Design, Chemistry, and Activity

  摘要：

  Arg-gingipains (Rgps) and Lys-gingipain (Kgp) are cysteine proteinases secreted by Porphyromonas gingivalis, the major pathogen implicated in periodontal disease. Gingipains are essential to the bacterium for its virulence and survival, and development of inhibitors targeting these proteins provides an approach to treat periodontal diseases. Here, we present the first example of structure-based design of gingipains inhibitors, with the use of the crystal structure of RgpB and the homology model of Kgp. Chloromethyl ketones were selected as suitable compounds to explore the specificity of the Sn binding region of both enzymes. Three series of inhibitors bearing Arg or Lys at P1 and different substituents at P2 and P3 were designed, synthesized, and tested. High potency (k(obs)/[I] similar to 10(7) M-1 s(-1)) was achieved for small ligands, such as the dipeptide analogues. The detailed analysis of Sn binding pockets revealed the molecular basis of inhibitory affinity and provided insight into the structure-activity relationship.

  DOI：

  10.1021/jm0600141
• 作为产物：
  描述：

  苄基叔丁基(7-重氮-6-氧代庚烷-1,5-二基)(S)-二氨基甲酸酯 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 50.0h， 生成 BocPhe-Phe-Lys(Z)-CH2Cl
  参考文献：
  名称：

  Exploring the Sn Binding Pockets in Gingipains by Newly Developed Inhibitors:  Structure-Based Design, Chemistry, and Activity

  摘要：

  Arg-gingipains (Rgps) and Lys-gingipain (Kgp) are cysteine proteinases secreted by Porphyromonas gingivalis, the major pathogen implicated in periodontal disease. Gingipains are essential to the bacterium for its virulence and survival, and development of inhibitors targeting these proteins provides an approach to treat periodontal diseases. Here, we present the first example of structure-based design of gingipains inhibitors, with the use of the crystal structure of RgpB and the homology model of Kgp. Chloromethyl ketones were selected as suitable compounds to explore the specificity of the Sn binding region of both enzymes. Three series of inhibitors bearing Arg or Lys at P1 and different substituents at P2 and P3 were designed, synthesized, and tested. High potency (k(obs)/[I] similar to 10(7) M-1 s(-1)) was achieved for small ligands, such as the dipeptide analogues. The detailed analysis of Sn binding pockets revealed the molecular basis of inhibitory affinity and provided insight into the structure-activity relationship.

  DOI：

  10.1021/jm0600141

文献信息

• Exploring the S<i>n</i> Binding Pockets in Gingipains by Newly Developed Inhibitors:  Structure-Based Design, Chemistry, and Activity
  作者：Arkadiusz Białas、Jolanta Grembecka、Daniel Krowarsch、Jacek Otlewski、Jan Potempa、Artur Mucha

  DOI：10.1021/jm0600141

  日期：2006.3.1

  Arg-gingipains (Rgps) and Lys-gingipain (Kgp) are cysteine proteinases secreted by Porphyromonas gingivalis, the major pathogen implicated in periodontal disease. Gingipains are essential to the bacterium for its virulence and survival, and development of inhibitors targeting these proteins provides an approach to treat periodontal diseases. Here, we present the first example of structure-based design of gingipains inhibitors, with the use of the crystal structure of RgpB and the homology model of Kgp. Chloromethyl ketones were selected as suitable compounds to explore the specificity of the Sn binding region of both enzymes. Three series of inhibitors bearing Arg or Lys at P1 and different substituents at P2 and P3 were designed, synthesized, and tested. High potency (k(obs)/[I] similar to 10(7) M-1 s(-1)) was achieved for small ligands, such as the dipeptide analogues. The detailed analysis of Sn binding pockets revealed the molecular basis of inhibitory affinity and provided insight into the structure-activity relationship.