Z-Val-Hyp(Bzl)-OH | 910469-88-4

• 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: Z-Val-Hyp(Bzl)-OH
• 英文别名: Cbz-Val-Hyp(Bn)(Bn)-OH；(2S,4R)-1-[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]-4-phenylmethoxypyrrolidine-2-carboxylic acid
• CAS: 910469-88-4
• 化学式: C₂₅H₃₀N₂O₆
• 分子量: 454.523
• InChiKey: ZACPRWBPUSOZET-FSSWDIPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Z-Val-Hyp(Bzl)-OH 在 palladium on activated charcoal 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、172.37 kPa 条件下， 反应 26.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[3-N'-[valyl-(2S,4R)-4-benzyloxyprolylamino]propyl]thymine]-3'-spiro-5''-[4''-amino-1'',2''-oxathiole-2'',2''-dioxide]
  参考文献：
  名称：

  Design and Discovery of a Novel Dipeptidyl-peptidase IV (CD26)-Based Prodrug Approach

  摘要：

  Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV ( DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline ( or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.

  DOI：

  10.1021/jm0606490
• 作为产物：
  描述：

  CBZ-L-缬氨酸 在 sodium hydroxide 、 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 Z-Val-Hyp(Bzl)-OH
  参考文献：
  名称：

  Design and Discovery of a Novel Dipeptidyl-peptidase IV (CD26)-Based Prodrug Approach

  摘要：

  Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV ( DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline ( or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.

  DOI：

  10.1021/jm0606490

文献信息

• Design and Discovery of a Novel Dipeptidyl-peptidase IV (CD26)-Based Prodrug Approach
  作者：Carlos García-Aparicio、María-Cruz Bonache、Ingrid De Meester、Ana San-Félix、Jan Balzarini、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1021/jm0606490

  日期：2006.8.1

  Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV ( DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline ( or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.