Boc-D-Ala-Ac₅c-OH

• 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-D-Ala-Ac₅c-OH
• 英文别名: 1-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]cyclopentane-1-carboxylic acid
• 化学式: C₁₄H₂₄N₂O₅
• 分子量: 300.355
• InChiKey: BEDXGQOLSMCWQT-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  环亮氨酸 在 sodium hydroxide 、 氯化亚砜 、 TEA 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 Boc-D-Ala-Ac₅c-OH
  参考文献：
  名称：

  Design and Synthesis of 1-Aminocycloalkane-1-carboxylic Acid-Substituted Deltorphin Analogues:  Unique δ and μ Opioid Activity in Modified Peptides

  摘要：

  Deltorphin analogues were substituted by a series of achiral C-alpha,C-alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carbaxylic acids, Ac(x)c, where (x) = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in deltorphin C, and in position 2 in [Ac(6)(c)2,- des-Phe(3)]deltorphin C hexapeptide. Receptor assays indicated that even though Ac(6)c(2) and Ac(6)c(3) exhibited a diminished K-i delta by ca. 20-fold (2.5-3.3 nM) relative to deltorphin C (K-i delta = 0.15 nM), selectivity was marginally elevated (K-i mu/K-i delta = 1250) or enhanced by about 70%, and both peptides fitted stringent iterative calculations for a two-site binding model (eta = 0.625 and 0.766, respectively, P < 0.0001). The disubstituted [Ac(6)c(2,3)]- or [Ac(6)c(2),des-Phe(3)]deltorphin analogues yielded peptides with decreased K-i delta, such that the latter peptide was essentially inactive. The presence of Ac(5)c or Ac(3)c in place of Phe(3) further diminished K-i delta (15.4 to 19.0 nM), yet delta selectivity only fell about one-half(K-i mu/K-i delta = 440 and 535, respectively), and only the former peptide fitted a two-site binding model (eta = 0.799). The replacement of Asp(4) by Ac(6)c, Ac5c, or Ac(3)c produced essentially nonselective analogues through the acquisition of high mu affinities (2.5, 0.58, and 0.27 nM, respectively) while maintaining high delta affinities (K-i delta = 0.045-0;054 nM) which were about 3 fold greater than that of deltorphin C. Using pharmacological assays in vitro (mouse vas deferens and guinea pig ileum), position 3-substituted analogues all indicated substantial losses in bioactivity, whereas substitution by 1-aminocycloalkanes at the fourth position retained high delta activity. In fact, the bioactivity of [Ac(3)c(4)]deltorphin C indicated a peptide with relatively weak delta selectivity, which was comparable to the observations with the receptor binding data. In summary, the data confirmed that (i) delta selectivity occurs in the absence of D-chirality at position 2, (ii) the aromaticity of Phe(3) is replaceable by an achiral residue with a hydrophobic ring-saturated side chain, and (iii) the acquisition of dual high-affinity analogues occurs through the elimination of the anionic function at position 4 and replacement by an amino acid with a hydrophobic side chain.

  DOI：

  10.1021/jm950490j

文献信息

• Design and Synthesis of 1-Aminocycloalkane-1-carboxylic Acid-Substituted Deltorphin Analogues:  Unique δ and μ Opioid Activity in Modified Peptides
  作者：Angela Breveglieri、Remo Guerrini、Severo Salvadori、Clementina Bianchi、Sharon D. Bryant、Martti Attila、Lawrence H. Lazarus

  DOI：10.1021/jm950490j

  日期：1996.1.1

  Deltorphin analogues were substituted by a series of achiral C-alpha,C-alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carbaxylic acids, Ac(x)c, where (x) = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in deltorphin C, and in position 2 in [Ac(6)(c)2,- des-Phe(3)]deltorphin C hexapeptide. Receptor assays indicated that even though Ac(6)c(2) and Ac(6)c(3) exhibited a diminished K-i delta by ca. 20-fold (2.5-3.3 nM) relative to deltorphin C (K-i delta = 0.15 nM), selectivity was marginally elevated (K-i mu/K-i delta = 1250) or enhanced by about 70%, and both peptides fitted stringent iterative calculations for a two-site binding model (eta = 0.625 and 0.766, respectively, P < 0.0001). The disubstituted [Ac(6)c(2,3)]- or [Ac(6)c(2),des-Phe(3)]deltorphin analogues yielded peptides with decreased K-i delta, such that the latter peptide was essentially inactive. The presence of Ac(5)c or Ac(3)c in place of Phe(3) further diminished K-i delta (15.4 to 19.0 nM), yet delta selectivity only fell about one-half(K-i mu/K-i delta = 440 and 535, respectively), and only the former peptide fitted a two-site binding model (eta = 0.799). The replacement of Asp(4) by Ac(6)c, Ac5c, or Ac(3)c produced essentially nonselective analogues through the acquisition of high mu affinities (2.5, 0.58, and 0.27 nM, respectively) while maintaining high delta affinities (K-i delta = 0.045-0;054 nM) which were about 3 fold greater than that of deltorphin C. Using pharmacological assays in vitro (mouse vas deferens and guinea pig ileum), position 3-substituted analogues all indicated substantial losses in bioactivity, whereas substitution by 1-aminocycloalkanes at the fourth position retained high delta activity. In fact, the bioactivity of [Ac(3)c(4)]deltorphin C indicated a peptide with relatively weak delta selectivity, which was comparable to the observations with the receptor binding data. In summary, the data confirmed that (i) delta selectivity occurs in the absence of D-chirality at position 2, (ii) the aromaticity of Phe(3) is replaceable by an achiral residue with a hydrophobic ring-saturated side chain, and (iii) the acquisition of dual high-affinity analogues occurs through the elimination of the anionic function at position 4 and replacement by an amino acid with a hydrophobic side chain.