Ile-Ala-Pro-Gly-Gly-Asn-Gly-Tyr

• 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: Ile-Ala-Pro-Gly-Gly-Asn-Gly-Tyr
• 英文别名: H-Ile-Ala-Pro-Gly-Gly-Asn-Gly-Tyr-OH；(2S)-2-[[2-[[(2S)-4-amino-2-[[2-[[2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]acetyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoic acid
• 化学式: C₃₃H₄₉N₉O₁₁
• 分子量: 747.806
• InChiKey: WFQWNWHTZCKFKW-ZPNFEQIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  53
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  322
• 氢给体数：
  10
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Ile-Ala-Pro-Gly-Gly-Asn-Gly-Tyr 在 0.1M aq. NaPO₄ 作用下， 生成 甘氨酰-L-酪氨酸 、 Ile-Ala-Pro-Gly-Gly-isoAsp-Gly-Tyr 、 Ile-Ala-Pro-Gly-Gly-(D-Asp)-Gly-Tyr 、 Ile-Ala-Pro-Gly-Gly-Asp-Gly-Tyr
  参考文献：
  名称：

  N5-Methylasparagine and asparagine as nucleophiles in peptides: main-chain vs. side-chain amide cleavage

  摘要：

  The chemistry of peptides containing N5-methylasparagine (NMA) was investigated by incubating the synthetic peptides Ile-Ala-Pro-Gly-Gly-Asn-Gly-Tyr and Ile-Ala-Pro-Gly-Gly-NMA-Gly-Tyr at 60-degrees-C in 0.1 M NaPO4, pH 7.4, to assay for peptide deamidation. The Asn-Gly octapeptide deamidates to Ile-Ala-Pro-Gly-Gly-isoAsp/Asp-Gly-Tyr with a half-life of 2.17 h and activation energy of 18.6 kcal/mol. The NMA-Gly octapeptide partitions between main-chain cleavage and side-chain deamidation in 2.7:1 ratio. Analysis of products diagnostic for each of these NMA peptide reactions yields indistinguishable activation energies for each pathway: 22.6 kcal/mol. The half-life for NMA side-chain deamidation is 98 h, commensurate with a 2.5 kcal/mol difference in activation free energies for deamidation at Asn and NMA sites. These results indicate that methylation provides a substantial (45-fold) stabilization against intramolecular C-N cleavage. The identical activation energy for the alternative pathways of NMA peptide reactivity suggests the differences in the rates may be due to the preexponential portion of the rate equation reflecting small differences in DELTAS(double dagger). Molecular mechanics studies were performed to account for these patterns. The computational studies disclose 3-fold more conformers in the Boltzmann population for the tetrahedral intermediate leading toward main-chain cleavage. This result supports the hypothesis that the 2.7-fold difference in NMA peptide partitioning rates is attributable to differences in DELTAS(double dagger).

  DOI：

  10.1021/jo00077a014

文献信息

• N5-Methylasparagine and asparagine as nucleophiles in peptides: main-chain vs. side-chain amide cleavage
  作者：Alan V. Klotz、Beth Ann Thomas

  DOI：10.1021/jo00077a014

  日期：1993.12

  The chemistry of peptides containing N5-methylasparagine (NMA) was investigated by incubating the synthetic peptides Ile-Ala-Pro-Gly-Gly-Asn-Gly-Tyr and Ile-Ala-Pro-Gly-Gly-NMA-Gly-Tyr at 60-degrees-C in 0.1 M NaPO4, pH 7.4, to assay for peptide deamidation. The Asn-Gly octapeptide deamidates to Ile-Ala-Pro-Gly-Gly-isoAsp/Asp-Gly-Tyr with a half-life of 2.17 h and activation energy of 18.6 kcal/mol. The NMA-Gly octapeptide partitions between main-chain cleavage and side-chain deamidation in 2.7:1 ratio. Analysis of products diagnostic for each of these NMA peptide reactions yields indistinguishable activation energies for each pathway: 22.6 kcal/mol. The half-life for NMA side-chain deamidation is 98 h, commensurate with a 2.5 kcal/mol difference in activation free energies for deamidation at Asn and NMA sites. These results indicate that methylation provides a substantial (45-fold) stabilization against intramolecular C-N cleavage. The identical activation energy for the alternative pathways of NMA peptide reactivity suggests the differences in the rates may be due to the preexponential portion of the rate equation reflecting small differences in DELTAS(double dagger). Molecular mechanics studies were performed to account for these patterns. The computational studies disclose 3-fold more conformers in the Boltzmann population for the tetrahedral intermediate leading toward main-chain cleavage. This result supports the hypothesis that the 2.7-fold difference in NMA peptide partitioning rates is attributable to differences in DELTAS(double dagger).