BOC-Asp(OBn)-Ala-NH2 | 302911-12-2

• 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-Asp(OBn)-Ala-NH2
• 英文别名: Boc-Asp(OBzl)-Ala-NH2；Boc-Asp(OBn)(OBn)-Ala-NH2；benzyl (3S)-4-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 302911-12-2
• 化学式: C₁₉H₂₇N₃O₆
• 分子量: 393.44
• InChiKey: FBIOPDHYVDVYDU-JSGCOSHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  BOC-Asp(OBn)-Ala-NH2 在 三乙胺 、 三氟乙酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 生成 BOC-Trp-Leu-Asp(OBn)-Ala-NH2
  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-天冬氨酸 4-苄酯 、 L-丙氨酰胺盐酸盐 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 以99%的产率得到BOC-Asp(OBn)-Ala-NH2
  参考文献：
  名称：

  合成Act系-肽支架的热力学和结构研究

  摘要：

  用相关的生物无机系统研究了分别处于氧化态+ VI和+ III的铀和euro的络合物。选择了三种具有不同结构特性的富含天冬氨酸的五肽进行研究，以理顺结构-亲和力关系。通过等温滴定量热法和时间分辨激光荧光光谱法交叉检验的热力学结果显示出不同的亲和力，取决于该肽对Eu（III）和U（VI）的亲和力。热力学方面与结构预测相关，结构预测通过密度泛函理论量子化学计算以及红外和扩展的X射线吸收精细结构实验获得。这些微观特性的结合表明，在p的情况下，羰基金属相互作用会影响熵，而较大的铀酰阳离子主要受预组织和空间效应的影响，因此亲和力通过焓得到增强。这里描述的方法揭示了控制肽in系元素亲和力的各种微观方面。强调这些机制当然应该有助于合理合成更高亲和力的仿生天冬氨酸配体。

  DOI：

  10.1021/acs.inorgchem.5b02379

文献信息

• 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.
• Thermodynamic and Structural Investigation of Synthetic Actinide–Peptide Scaffolds
  作者：Samir Safi、Aurélie Jeanson、Jérome Roques、Pier Lorenzo Solari、Florence Charnay-Pouget、Christophe Den Auwer、Gaëlle Creff、David J. Aitken、Eric Simoni

  DOI：10.1021/acs.inorgchem.5b02379

  日期：2016.1.19

  peptide for both Eu(III) and U(VI). The thermodynamic aspects were correlated to structural predictions, which were acquired by density functional theory quantum chemical calculations and from IR and extended X-ray absorption fine structure experiments. The combination of these microscopic properties revealed that carbonyl–metal interactions affected the entropy in the case of europium, while the larger

  用相关的生物无机系统研究了分别处于氧化态+ VI和+ III的铀和euro的络合物。选择了三种具有不同结构特性的富含天冬氨酸的五肽进行研究，以理顺结构-亲和力关系。通过等温滴定量热法和时间分辨激光荧光光谱法交叉检验的热力学结果显示出不同的亲和力，取决于该肽对Eu（III）和U（VI）的亲和力。热力学方面与结构预测相关，结构预测通过密度泛函理论量子化学计算以及红外和扩展的X射线吸收精细结构实验获得。这些微观特性的结合表明，在p的情况下，羰基金属相互作用会影响熵，而较大的铀酰阳离子主要受预组织和空间效应的影响，因此亲和力通过焓得到增强。这里描述的方法揭示了控制肽in系元素亲和力的各种微观方面。强调这些机制当然应该有助于合理合成更高亲和力的仿生天冬氨酸配体。