Val-Val-Gly-NH2 | 131131-28-7

• 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: Val-Val-Gly-NH2
• 英文别名: (2S)-2-amino-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxobutan-2-yl]-3-methylbutanamide
• CAS: 131131-28-7
• 化学式: C₁₂H₂₄N₄O₃
• 分子量: 272.348
• InChiKey: QCTKYQVSGVBMEU-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  127
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Val-Val-Gly-NH2 在 N-甲基吗啉 、 N-甲基吗啉盐酸盐 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 Boc-Tyr-D-Ala-Phe-Asp(OBn)(OBn)-Val-Val-Gly-NH2
  参考文献：
  名称：

  Unique sequence in deltorphin C confers structural requirement for δ opioid receptor selectivity

  摘要：

  A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site.

  DOI：

  10.1016/0223-5234(92)90113-f
• 作为产物：
  描述：

  Boc-L-缬氨酸羟基琥珀酰亚胺酯 在 N-甲基吗啉 、 苯甲醚 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 Val-Val-Gly-NH2
  参考文献：
  名称：

  Marastoni; Salvadori; Balboni, Arzneimittel-Forschung/Drug Research, 1995, vol. 45, # 2, p. 116 - 119

  摘要：

  DOI：

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.
• SALVADORI, SEVERO;MARASTONI, MAURO;BALBONI, GIANFRANCO;BOREA, PIER ANDREA+, J. MED. CHEM., 34,(1991) N, C. 1656-1661
  作者：SALVADORI, SEVERO、MARASTONI, MAURO、BALBONI, GIANFRANCO、BOREA, PIER ANDREA+

  DOI：——

  日期：——