[(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-acetic acid | 27450-98-2

• 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: [(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-acetic acid
• 英文别名: Boc-Val-Leu-Gly-OH；2-[[(2S)-4-methyl-2-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]pentanoyl]amino]acetic acid
• CAS: 27450-98-2
• 化学式: C₁₈H₃₃N₃O₆
• 分子量: 387.477
• InChiKey: KJTAHHAFVWPZKQ-JSGCOSHPSA-N

物化性质

• 沸点：
  638.1±50.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-acetic acid 在 1-羟基苯并三唑 、 二乙胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.33h， 生成 tert-butyl N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(9-ethylcarbazol-3-yl)amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Peptide derivatives specific for a Plasmodium falciparum proteinase inhibit the human erythrocyte invasion by merozoites

  摘要：

  A specific proteinase of P. falciparum merozoites has been detected by using hydrosoluble fluorogenic peptidic substrates synthesized by classical peptide chemistry; their N-terminal end was acylated by a gluconoyl group that protects them from aminopeptidase degradation and increases their hydrosolubility, and their carboxylic end was substituted by a 3-amino-9-ethylcarbazole group. The sequence Val-Leu-Gly-Lys was found to be the most specific substrate. On this basis, reversible peptidic inhibitors were synthesized by substituting the C-terminal lysyl residue, at the proteolytic site, by different alkylamines and amino alcohols. The activity of these compounds, studied on the P. falciparum proteinase and in in vitro cultures, strongly suggests a specific effect of this peptidic sequence on the reinvasion process. The peptidic inhibitors do not impair the release of merozoites from schizonts, but selectively inhibit the invasion step leading to the formation of rings. Although the natural target of this enzyme is not yet known, these specific peptide inhibitors could lead to a new antimalarial approach.

  DOI：

  10.1021/jm00114a011
• 作为产物：
  描述：

  Glycine, N-[N-[N-[(1,1-dimethylethoxy)carbonyl]-L-valyl]-L-leucyl]-,phenylmethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 [(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-acetic acid
  参考文献：
  名称：

  Peptide derivatives specific for a Plasmodium falciparum proteinase inhibit the human erythrocyte invasion by merozoites

  摘要：

  A specific proteinase of P. falciparum merozoites has been detected by using hydrosoluble fluorogenic peptidic substrates synthesized by classical peptide chemistry; their N-terminal end was acylated by a gluconoyl group that protects them from aminopeptidase degradation and increases their hydrosolubility, and their carboxylic end was substituted by a 3-amino-9-ethylcarbazole group. The sequence Val-Leu-Gly-Lys was found to be the most specific substrate. On this basis, reversible peptidic inhibitors were synthesized by substituting the C-terminal lysyl residue, at the proteolytic site, by different alkylamines and amino alcohols. The activity of these compounds, studied on the P. falciparum proteinase and in in vitro cultures, strongly suggests a specific effect of this peptidic sequence on the reinvasion process. The peptidic inhibitors do not impair the release of merozoites from schizonts, but selectively inhibit the invasion step leading to the formation of rings. Although the natural target of this enzyme is not yet known, these specific peptide inhibitors could lead to a new antimalarial approach.

  DOI：

  10.1021/jm00114a011

文献信息

• Critical Peptide Size for Insolubility Caused by a β-Sheet Aggregation and Solubility Improvement in Hydrophobic Peptides by Replacement of Alanine Residues with α-Aminoisobutyric Acid Residues
  作者：Mitsuaki Narita、Junn-Yann Chen、Hiroyuki Sato、Yukio Kim

  DOI：10.1246/bcsj.58.2494

  日期：1985.9

  In order to demonstrate an important role of a β-sheet aggregation on insolubility of peptides, hydrophobic peptides having partial amino acid sequences found in natural proteins have been prepared by the step-wise elongation and fragment condensation methods. In conformity with the solubility prediction for protected peptides in our previous paper, solubility data indicate that insolubility of peptides appears to begin at octa- or nonapeptide levels. In hydrophobic sequences found in proteins, the structure of peptide backbones, namely, the β-structure clearly plays an important role on insolubility of peptides, but the composition of peptides does not. Solubility improvement in hydrophobic peptides included in α-helical regions of proteins is easily achieved by replacement of Ala residues with Aib residues. High solubility of the peptides containing Aib residues is clearly explained by the observation that replacement of Cα hydrogen atoms with methyl groups greatly disturbs β-sheet structures, promoting helical folding in peptides. The great ability of an Aib residue to promote helical folding is distinctly revealed in the peptide fragments included in α-helical regions of proteins as demonstrated before in model oligo(Leu)s.

  为了证明β-折叠聚集对肽不溶性的重要作用，通过逐步延伸和片段缩合方法制备了具有天然蛋白质中发现的部分氨基酸序列的疏水性肽。与我们之前论文中受保护肽的溶解度预测一致，溶解度数据表明肽的不溶性似乎从八肽或九肽水平开始。在蛋白质中发现的疏水序列中，肽骨架的结构，即β-结构显然对肽的不溶性起着重要作用，但肽的组成却没有。通过用 Aib 残基替换 Ala 残基，可以轻松提高蛋白质 α 螺旋区域中疏水性肽的溶解度。含有 Aib 残基的肽的高溶解度可以通过观察到用甲基取代 Cα 氢原子极大地扰乱 β-折叠结构、促进肽中的螺旋折叠来清楚地解释。 Aib 残基促进螺旋折叠的强大能力在蛋白质 α 螺旋区域中包含的肽片段中得到了明显的体现，如之前在模型寡 (Leu) 中所证明的那样。
• Polypeptide derivatives and calcium metabolism improving agent
  申请人：Otsuka Pharmaceutical Co., Ltd.

  公开号：US05204326A1

  公开（公告）日：1993-04-20

  Novel polypeptide derivatives, acid-addition salts thereof and complexes thereof, having the activities for inhibiting bone calcium absorption, for lowering the blood level of calcium, as analgesics, for inhibiting secretion of the gastric juice. Pharmaceutical composition can be prepared by formulating, at least one of the novel polypeptide derivatives, acid-addition salts thereof and complexes thereof, together with a proteolytic enzyme inhibitors and/or pharmaceutically acceptable acids. The pharmaceutical composition are quite effective as agents for curing hypercalcemia, for curing Peget's disease, for curing osteoporosis, analgetic agent, anti-ulcerative agent and the like.

  新型多肽衍生物及其酸加成盐和配合物，具有抑制骨钙吸收、降低血钙水平、作为镇痛剂和抑制胃酸分泌的活性。可以通过将至少一种新型多肽衍生物、其酸加成盐和配合物与蛋白酶抑制剂和/或药用酸一起制剂而成制备药物组合物。该药物组合物对治疗高钙血症、治疗佩吉特病、治疗骨质疏松症、镇痛剂、抗溃疡剂等方面具有相当有效的作用。
• CAKATA, JOSITSUGU;KITA, MASAAKI
  作者：CAKATA, JOSITSUGU、KITA, MASAAKI

  DOI：——

  日期：——
• SHIBA, TETSUO;TESHIMA, TADASHI;NAKAI, TAKAHISA;KITAZAWA, MANABU, TETRAHEDRON, 44,(1988) N 3, 787-803
  作者：SHIBA, TETSUO、TESHIMA, TADASHI、NAKAI, TAKAHISA、KITAZAWA, MANABU

  DOI：——

  日期：——