Z-L-Leu-L-His | 79778-48-6

• 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: Z-L-Leu-L-His
• 英文别名: N-[(Benzyloxy)carbonyl]-L-leucyl-L-histidine；(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]propanoic acid
• CAS: 79778-48-6
• 化学式: C₂₀H₂₆N₄O₅
• 分子量: 402.45
• InChiKey: OLKSMTLZDPXSRI-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Z-L-Leu-L-His 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.

  DOI：

  10.1021/jm9800696
• 作为产物：
  描述：

  N-苄氧羰基-L-亮氨酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 为溶剂， 生成 Z-L-Leu-L-His
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.

  DOI：

  10.1021/jm9800696
• 作为试剂：
  描述：

  2-Benzyloxycarbonylamino-propionic acid 4-nitro-phenyl ester 在 Z-L-Leu-L-His 作用下， 以 various solvent(s) 为溶剂， 生成 N-benzyloxycarbonyl-D-alanine 、 苄氧羰基-L-丙氨酸
  参考文献：
  名称：

  改性线性聚（乙烯亚胺）结构域中氨基酸酯的立体选择性水解

  摘要：

  N-癸酰基-L-组氨酸(2a) 和线性聚(亚乙基亚胺) 衍生物域中含有L-组氨酸残基的二肽(2b) 催化的水解中表现出较大的速率增强和立体选择性偏好。

  DOI：

  10.1246/cl.1984.433

文献信息

• Vlasov, G. P.; Glushenkova, V. R.; Glinskaya, I. V., Journal of general chemistry of the USSR, 1987, vol. 57, p. 1895 - 1901
  作者：Vlasov, G. P.、Glushenkova, V. R.、Glinskaya, I. V.、Nadezhina, L. B.、Komogorova, T. A.、Ditkovskaya, I. B.

  DOI：——

  日期：——
• VLASOV, G. P.;GLUSHENKOVA, V. R.;GLINSKAYA, O. V.;NADEZHDINA, L. B.;KOMOG+, ZH. OBSHCH. XIMII, 57,(1987) N 9, 2117-2124
  作者：VLASOV, G. P.、GLUSHENKOVA, V. R.、GLINSKAYA, O. V.、NADEZHDINA, L. B.、KOMOG+

  DOI：——

  日期：——
• A catalyst for asymmetric induction
  申请人：SUMITOMO CHEMICAL COMPANY LIMITED

  公开号：EP0420658B1

  公开（公告）日：1995-08-30
• US6204406B1
  申请人：——

  公开号：US6204406B1

  公开（公告）日：2001-03-20
• Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies
  作者：Peter S. Dragovich、Stephen E. Webber、Robert E. Babine、Shella A. Fuhrman、Amy K. Patick、David A. Matthews、Siegfried H. Reich、Joseph T. Marakovits、Thomas J. Prins、Ru Zhou、Jayashree Tikhe、Ethel S. Littlefield、Ted M. Bleckman、Michael B. Wallace、Thomas L. Little、Clifford E. Ford、James W. Meador、Rose Ann Ferre、Edward L. Brown、Susan L. Binford、Dorothy M. DeLisle、Stephen T. Worland

  DOI：10.1021/jm9800696

  日期：1998.7.1

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.