H-Ala-Ala-Lys-Ala-Gly-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: H-Ala-Ala-Lys-Ala-Gly-OH
• 英文别名: Ala-Ala-Lys-Ala-Gly-OH；Ala-Ala-Lys-Ala-Gly；AAKAG；2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoyl]amino]hexanoyl]amino]propanoyl]amino]acetic acid
• 化学式: C₁₇H₃₂N₆O₆
• 分子量: 416.478
• InChiKey: HGUCJKALLRPARX-BJDJZHNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  206
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Bz-L-Phe-OGp 、 H-Ala-Ala-Lys-Ala-Gly-OH 在 K₆₀E,D₁₈₉S,D₁₉₄N mutant trypsin HEPES buffer 、 sodium chloride 、 calcium chloride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以75.1%的产率得到Bz-Phe-Ala-Ala-Lys-Ala-Gly-OH
  参考文献：
  名称：

  Substrate Mimetics-Specific Peptide Ligases:  Studies on the Synthetic Utility of a Zymogen and Zymogen-Like Enzymes

  摘要：

  Although proteases are capable of synthesizing peptide bonds, they are not proficient at peptide fragment ligation. Further manipulations are needed to shift the native enzyme activity from the cleavage to the synthesis of peptides. This account reports on the synthetic potential of nonactivatable trypsinogen and zymogen-like enzymes designed to minimize proteolytic side reactions during peptide synthesis.

  DOI：

  10.1021/jo026117i

文献信息

• Enzymatic Coupling of Specific Peptides at Nonspecific Ligation Sites:  Effect of Asp189Glu Mutation in Trypsin on Substrate Mimetic-Mediated Reactions
  作者：Shaojun Xu、Kathrin Rall、Frank Bordusa

  DOI：10.1021/jo001243c

  日期：2001.3.1

  reactions using substrate mimetics as the acyl donor and specific amino acid-containing peptides as the acyl acceptor. The competition assay verifies the predicted shift in substrate preference from Lys and Arg to the substrate mimetics and, thus, from cleavage to synthesis of peptide bonds. The combination of results obtained qualifies the trypsin mutant D189E as the first substrate mimetic-specific

  两个主要缺点严重限制了蛋白酶在肽片段偶联中作为试剂的合成价值：（i）天然的蛋白水解活性，因此存在不希望的肽裂解的风险；（ii）有限的酶特异性限制了可在其间形成肽键的氨基酸残基。尽管可以通过使用在非特异性连接位点实现肽键形成的底物模拟物来克服后者，但仍然存在蛋白水解裂解的风险，这阻碍了这种强有力的肽偶联策略的广泛接受。本文报道了胰蛋白酶点突变体Asp189Glu对底物模拟介导的反应的影响。研究了这种突变对4-胍基苯基酯类型的底物模拟物的稳态水解以及胰蛋白酶特异性的含有Lys和Arg的肽的影响。通过使用底物模拟物作为酰基供体和含特定氨基酸的肽作为酰基受体的酶促偶联反应证实了结果。竞争分析验证了底物偏好从Lys和Arg到底物模拟物的预测转变，从而验证了从裂解到肽键合成的转变。获得的结果的组合使胰蛋白酶突变体D189E成为第一个底物模拟物特异性肽连接酶。竞争分析验证了底物偏好从Lys和Arg到底物
• Substrate Mimetics and Freezing Strategy:  A Useful Combination That Broadens the Scope of Proteases for Synthesis
  作者：Nicole Wehofsky、Sebastian W. Kirbach、Marion Haensler、Johannes-Dieter Wissmann、Frank Bordusa

  DOI：10.1021/ol005867g

  日期：2000.7.1

  [reaction: see text] We present an irreversible and efficient protease-based method for peptide synthesis which occurs independently of the primary specificity of proteases and also without proteolytic side reactions. The key feature of this approach is the combination of the substrate mimetics strategy with frozen state enzymology. Model reactions catalyzed by several proteases qualify this approach

  [反应：参见正文]我们提出了一种不可逆且有效的基于蛋白酶的肽合成方法，该方法独立于蛋白酶的主要特异性而发生，并且没有蛋白水解副反应。该方法的关键特征是底物模拟策略与冷冻状态酶学的结合。由几种蛋白酶催化的模型反应将这种方法作为一种强有力的概念，朝着更广泛地应用蛋白酶作为肽连接生物催化剂的方向发展。
• Effect of freezing on the enzymatic coupling of specific amino acid-containing peptide fragments
  作者：Nicole Wehofsky、Marion Haensler、Sebastian W Kirbach、Johannes-Dieter Wissmann、Frank Bordusa

  DOI：10.1016/s0957-4166(00)00187-7

  日期：2000.6

  The effect of freezing on the enzymatic coupling of highly specific amino acid-containing peptide fragments was investigated using trypsin, a-chymotrypsin, and Bacillus licheniformis Glu-specific endopeptidase as biocatalysts. Comparison with reactions at normal temperature indicates that freezing efficiently represses the cleavage of specific peptide bonds independent of their individual localisation and specificity achieving irreversible and efficient peptide bond formation without proteolytic side reactions. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Substrate Mimetics-Specific Peptide Ligases:  Studies on the Synthetic Utility of a Zymogen and Zymogen-Like Enzymes
  作者：Kathrin Rall、Frank Bordusa

  DOI：10.1021/jo026117i

  日期：2002.12.1

  Although proteases are capable of synthesizing peptide bonds, they are not proficient at peptide fragment ligation. Further manipulations are needed to shift the native enzyme activity from the cleavage to the synthesis of peptides. This account reports on the synthetic potential of nonactivatable trypsinogen and zymogen-like enzymes designed to minimize proteolytic side reactions during peptide synthesis.