Boc-Trp-Leu-OH | 70706-54-6

• 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: Boc-Trp-Leu-OH
• 英文别名: BOC-Trp-Leu-H；Boc-WL-OH；(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-4-methylpentanoic acid
• CAS: 70706-54-6
• 化学式: C₂₂H₃₁N₃O₅
• 分子量: 417.505
• InChiKey: GYFUMABWFMAEBC-ROUUACIJSA-N

物化性质

• 沸点：
  694.8±55.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Trp-Leu-OH 在 10percent Pd/C 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙二醇二甲醚 为溶剂， 反应 4.0h， 生成 (S)-3-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-4-methyl-pentanoylamino}-N-((S)-1-carbamoyl-ethyl)-succinamic acid
  参考文献：
  名称：

  Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists

  摘要：

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.

  DOI：

  10.1021/jm000937a
• 作为产物：
  描述：

  Boc-L-Trp-L-Leu-OMe 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 Boc-Trp-Leu-OH
  参考文献：
  名称：

  肽模拟物作为有效的双重 SARS-CoV-2 组织蛋白酶-L 和主要蛋白酶抑制剂：计算机设计、合成和药理学表征

  摘要：

  在本文中，我们介绍了一系列新的拟肽作为有效的 SARS-CoV-2 药物的设计、合成和生物学评价。从我们之前描述的主蛋白酶 (M) 和木瓜蛋白酶样蛋白酶 (PL) 双重抑制剂开始，我们在此公开了其对 SARS-CoV 的新兴靶点组织蛋白酶 L (CTSL) 的高抑制活性 (IC = 19.80 ± 4.44 nM) -2感染机器。受 结构启发的一项设计导致了肽模拟物库的开发，该库显示出针对 CTSL 和 M 的有趣活性，使我们能够追踪与这两种酶结合的化学要求。对感染 5 种不同 SARS-CoV-2 变体的 Vero 细胞进行的筛选突出显示了大多数合成化合物 (、、、和) 的亚微摩尔活性，与酶抑制测定结果一致。这些化合物对几种不同的 RNA 病毒缺乏活性，除了 229E 和 OC43 人类冠状病毒株外，其特征还在于组织蛋白酶-L 依赖性释放到宿主细胞中。还评估了最有前途的衍生物的化学和代谢

  DOI：

  10.1016/j.ejmech.2024.116128

文献信息

• Studies on peptides. CVIII. Synthesis of the protected eicosapeptide corresponding to positions 19 to 38 of human parathyroid hormone.
  作者：SUSUMU FUNAKOSHI、HARUAKI YAJIMA

  DOI：10.1248/cpb.30.1697

  日期：——

  As a starting material for the synthesis of human parathyroid hormone (1-38), a C-terminal-protected eicosapeptide ester (positions 19-38) was synthesized by successive condensation of four peptide fragments; (positions 29-38), (25-28), (22-24) and (19-21).

  作为合成人甲状旁腺激素（1-38）的起始原料，通过连续缩合（29-38 位）、（25-28 位）、（22-24 位）和（19-21 位）四个肽段，合成了一个 C 端保护的二十肽酯（19-38 位）。
• US4997950A
  申请人：——

  公开号：US4997950A

  公开（公告）日：1991-03-05
• Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists
  作者：Caroline M. R. Low、James W. Black、Howard B. Broughton、Ildiko M. Buck、Jonathan M. R. Davies、David J. Dunstone、Robert A. D. Hull、S. Barret Kalindjian、Iain M. McDonald、Michael J. Pether、Nigel P. Shankley、Katherine I. M. Steel

  DOI：10.1021/jm000937a

  日期：2000.9.1

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.
• Peptidomimetics as potent dual SARS-CoV-2 cathepsin-L and main protease inhibitors: In silico design, synthesis and pharmacological characterization
  作者：Tania Ciaglia、Vincenzo Vestuto、Veronica Di Sarno、Simona Musella、Gerardina Smaldone、Francesca Di Matteo、Valeria Napolitano、Maria Rosaria Miranda、Giacomo Pepe、Manuela Giovanna Basilicata、Sara Novi、Ilaria Capolupo、Giuseppe Bifulco、Pietro Campiglia、Isabel Gomez-Monterrey、Robert Snoeck、Graciela Andrei、Michele Manfra、Carmine Ostacolo、Gianluigi Lauro、Alessia Bertamino

  DOI：10.1016/j.ejmech.2024.116128

  日期：2024.2

  highlighted sub-micromolar activities for most of the synthesized compounds (, , , and ) in agreement with the enzymatic inhibition assays results. The compounds showed lack of activity against several different RNA viruses except for the 229E and OC43 human coronavirus strains, also characterized by a cathepsin-L dependent release into the host cells. The most promising derivatives were also evaluated

  在本文中，我们介绍了一系列新的拟肽作为有效的 SARS-CoV-2 药物的设计、合成和生物学评价。从我们之前描述的主蛋白酶 (M) 和木瓜蛋白酶样蛋白酶 (PL) 双重抑制剂开始，我们在此公开了其对 SARS-CoV 的新兴靶点组织蛋白酶 L (CTSL) 的高抑制活性 (IC = 19.80 ± 4.44 nM) -2感染机器。受 结构启发的一项设计导致了肽模拟物库的开发，该库显示出针对 CTSL 和 M 的有趣活性，使我们能够追踪与这两种酶结合的化学要求。对感染 5 种不同 SARS-CoV-2 变体的 Vero 细胞进行的筛选突出显示了大多数合成化合物 (、、、和) 的亚微摩尔活性，与酶抑制测定结果一致。这些化合物对几种不同的 RNA 病毒缺乏活性，除了 229E 和 OC43 人类冠状病毒株外，其特征还在于组织蛋白酶-L 依赖性释放到宿主细胞中。还评估了最有前途的衍生物的化学和代谢