2-(3-甲基哌嗪-1-基)吡啶-3-羧酸 | 105760-58-5

• 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
• 中文名称: 2-(3-甲基哌嗪-1-基)吡啶-3-羧酸
• 中文别名: (2S)-2-[[2-[[(2S)-4-氨基-2-[[(2S)-1-[(2S)-2-[[(2S)-2-氨基-3-甲基丁酰基]氨基]-3-(4-羟基苯基)丙酰]吡咯烷-2-羰基]氨基]-4-氧代丁酰基]氨基]乙酰基]氨基]丙酸
• 英文名称: L-Val-L-Tyr-L-Pro-L-Asn-Gly-L-Ala
• 英文别名: Valyl-tyrosyl-prolyl-asparaginyl-glycyl-alanine；(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]acetyl]amino]propanoic acid
• CAS: 105760-58-5
• 化学式: C₂₈H₄₁N₇O₉
• 分子量: 619.675
• InChiKey: DERJZRCOKJPFBB-GJLLLRFJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  263
• 氢给体数：
  8
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 2-(3-甲基哌嗪-1-基)吡啶-3-羧酸 以 1,4-二氧六环 、 水 为溶剂， 反应 0.33h， 生成 N-acetyl-(L-Val-L-Tyr-L-Pro-L-Asn-Gly-L-Ala)
  参考文献：
  名称：

  固态肽与聚乙烯吡咯烷酮的反应

  摘要：

  在高温（70摄氏度）和低相对湿度（大约0％）的稳定性研究中，从固体聚乙烯吡咯烷酮（PVP）基质中回收含天冬酰胺的六肽（VYPNGA）及其已知的脱酰胺产物是不完全的。为了确定这种质量损失的原因，通过冻干包含PVP，甘油和Asn-六肽的溶液在pH 7.5磷酸盐缓冲液中，然后在70°C和0％相对湿度下储存，来制备制剂。Asn-六肽损失是单指数的，并在剩余约30％时达到平稳状态。肽及其已知的脱酰胺产物的总回收率约为肽负载量的30％。具有荧光检测的尺寸排阻色谱法表明在6 M盐酸胍存在下稳定的PVP肽加合物的形成。使用N-乙酰基苯丙氨酸，苯丙氨酸乙酯和N-乙酰基酪氨酸乙酯进行的相似稳定性研究表明，该反应涉及N末端肽。在羧肽酶-A的存在下，加合物被破坏，表明在肽和PVP之间形成了酰胺键。（15）使用（15）N标记的缬氨酸作为肽N端的模型的N固态核磁共振波谱显示（15）N的不同种群，这表明在酰胺键形成之前

  DOI：

  10.1002/jps.10316
• 作为试剂：
  描述：

  tris(hydroxymethyl)aminomethane 在 poly(vinylpyrrolidone) 、 甘油 、 2-(3-甲基哌嗪-1-基)吡啶-3-羧酸 作用下， 以 水 为溶剂， 生成 聚合甲醛
  参考文献：
  名称：

  肽制剂中的Tris缓冲液在高温下产生甲醛。

  摘要：

  该技术说明为在高温（70摄氏度）下储存的肽制剂中Tris缓冲液的降解提供了证据。缓冲液降解释放出甲醛，甲醛与酪氨酸残基反应。那些参与肽/蛋白质配制的人员应该意识到这种常见的生物缓冲液可能存在的不稳定性。

  DOI：

  10.1002/jps.1073

文献信息

• Effect of ‘pH’ on the rate of asparagine deamidation in polymeric formulations: ‘pH’–rate profile
  作者：Yuan Song、Richard L. Schowen、Ronald T. Borchardt、Elizabeth M. Topp

  DOI：10.1002/1520-6017(200102)90:2<141::aid-jps5>3.0.co;2-y

  日期：2001.2

  solids under neutral conditions (6 < 'pH' < 8). In solution, the reaction exhibited general base catalysis for 'pH' > 8, whereas the reaction was 'pH'-independent in the polymeric solids in this range. The 'pH'-rate profile and supporting buffer catalysis data are consistent with a change in the rate-determining step in the basic range from 'pH'-dependent attack of the deprotonated backbone amide nitrogen

  测量了在玻璃状和橡胶状聚合物中模型六肽（L-Val-L-Tyr-L-Pro-L-Asn-Gly-L-Ala）的Asn脱酰胺率与有效pH（'pH'）的关系含聚乙烯吡咯烷酮（PVP）的固体，并在70℃的溶液中控制。反应在宽的“ pH”范围内（0.5 <“ pH” <12）在所有样品中均表现出伪一级动力学；相似产物的形成表明反应机理不受基质类型的影响。在酸性范围内（“ pH” <4），聚合物和溶液样品的脱酰胺速率相当。在中性“ pH”（6 <“ pH” <8）下，溶液状态速率比聚合固体中的状态速率快，在碱性范围（“ pH”> 8）下增加到10,000倍。在中性条件下（6 <'pH'<8），在溶液和聚合物固体中观察到特定的碱催化作用。在溶液中，对于“ pH”> 8，该反应表现出一般的碱催化作用，而在此范围内，该反应在聚合物固体中不依赖于“ pH”。“ pH”速率曲线和辅助缓冲液催化数据与速率确定步
• Controlling deamidation rates in a model peptide: Effects of temperature, peptide concentration, and additives
  作者：Lewis P. Stratton、R.Michael Kelly、Jared Rowe、Jesse E. Shively、D.David Smith、John F. Carpenter、Mark C. Manning

  DOI：10.1002/jps.1165

  日期：2001.12

  The rate of deamidation of the Asn residue in Val-Tyr-Pro-Asn-Gly-Ala (VYPNGA), a model peptide, was determined at pH 9 (400 mM Tris buffer) as a function of temperature and peptide concentration. Over the temperature range 5-65 degrees C, deamidation followed Arrhenius behavior, with an apparent activation energy of 13.3 kcal/mol. Furthermore, increasing the peptide concentration slows the rate of

  在pH 9（400 mM Tris缓冲液）下，根据温度和肽浓度，确定模型肽Val-Tyr-Pro-Asn-Gly-Ala（VYPNGA）中Asn残基的脱酰胺速率。在5-65摄氏度的温度范围内，脱酰胺作用遵循Arrhenius行为，表观活化能为13.3 kcal / mol。此外，增加肽浓度减慢了脱酰胺的速度。以前尚未报道过脱酰胺的自我稳定作用。在存在蔗糖和泊洛沙姆407（Pluronic F127）的情况下，也确定了脱酰胺的速率。在这两种情况下，脱酰胺率在35摄氏度下最多可延迟40％。在含有泊洛沙姆407的水溶液中，稳定度与可逆热固性凝胶的形成无关。用蔗糖 脱酰胺率的最大降低幅度仅为5％（w / v）。蔗糖的添加导致对于II型β-转角结构的构象偏好更大，据推测，其不易发生分子内环化和随后的脱酰胺作用。
• Chemical stability of peptides in polymers. 2. Discriminating between solvent and plasticizing effects of water on peptide deamidation in poly(vinylpyrrolidone)
  作者：Mei C. Lai、Michael J. Hageman、Richard L. Schowen、Ronald T. Borchardt、Brian B. Laird、Elizabeth M. Topp

  DOI：10.1021/js9802289

  日期：1999.10

  The mechanistic role of water in the deamidation of a model asparagine-containing hexapeptide (Val-Tyr-Pro-Asn-Gly-Ala) in lyophilized formulations containing poly(vinylpyrrolidone) (PVP) and glycerol was investigated. Glycerol was used as a plasticizer to vary formulation glass transition temperature (T-g) without significantly changing water content or activity. Increases in moisture and glycerol contents increased the rate of peptide deamidation. This increase was strongly correlated with T-g at constant water content and activity, suggesting that increased matrix mobility facilitates deamidation. In rubbery systems (T > T-g), deamidation rates appeared to be independent of water content and activity in formulations with similar T(g)s. However, in glassy formulations with similar T(g)s, deamidation increased with water content, suggesting a solvent/medium effect of water on reactivity in this regime. An increase in water content also affected the degradation product distribution; less of the cyclic imide intermediate and more of the hydrolytic products, isoAsp- and Asphexapeptides, were observed as water content increased. Thus, residual water appears to facilitate deamidation in these solid PVP formulations both by enhancing molecular mobility and by solvent/medium effects, and also participates as a chemical reactant in the subsequent breakdown of the cyclic imide.
• Chemical stability of peptides in polymers. 1. Effect of water on peptide deamidation in poly(vinyl alcohol) and poly(vinyl pyrrolidone) matrixes
  作者：Mei C. Lai、Michael J. Hageman、Richard L. Schowen、Ronald T. Borchardt、Elizabeth M. Topp

  DOI：10.1021/js980227g

  日期：1999.10

  This paper examines the effect of water content, water activity, and glass transition temperature (T-g) on the deamidation of an asparagine-containing hexapeptide (VYPNGA; Asn-hexapeptide) in lyophilized poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) at 50 degrees C. The rate of Asn-hexapeptide deamidation increases with increasing water content or water activity and, hence, decreasing T-g. The rate of deamidation is more sensitive to changes in these parameters in PVA than in PVP. Deamidation is clearly evident in the glassy state in both formulations, In the glassy state, the peptide is more stable in PVA than in PVP formulations but is less stable in the rubbery state. No single variable (water content, water activity, or T-g) could account for the variation in deamidation rates in PVA and PVP formulations. Deamidation rates were correlated with the degree of plasticization by water (distance of T-g from the dry intrinsic glass transition temperature); coincident curves for the two polymers were obtained with this correlation. Deamidation in PVA and PVP was closely correlated with the extent of water-induced plasticization experienced by the formulation relative to its glass transition at 50 degrees C, suggesting that the physical stale of formulations could be used to predict chemical stability.
• Reaction of a Peptide with Polyvinylpyrrolidone in the Solid State
  作者：Ajit Joseph M. D'Souza、Richard L. Schowen、Ronald T. Borchardt、Jonathon S. Salsbury、Eric J. Munson、Elizabeth M. Topp

  DOI：10.1002/jps.10316

  日期：2003.3

  N-terminus. The adduct was disrupted in the presence of carboxypeptidase-A, suggesting the formation of an amide bond between the peptide and PVP. (15)N solid-state nuclear magnetic resonance spectroscopy using (15)N-labeled valine as a model of the peptide N-terminus showed different populations of (15)N, suggesting that noncovalent peptide-polymer interactions precede amide bond formation.

  在高温（70摄氏度）和低相对湿度（大约0％）的稳定性研究中，从固体聚乙烯吡咯烷酮（PVP）基质中回收含天冬酰胺的六肽（VYPNGA）及其已知的脱酰胺产物是不完全的。为了确定这种质量损失的原因，通过冻干包含PVP，甘油和Asn-六肽的溶液在pH 7.5磷酸盐缓冲液中，然后在70°C和0％相对湿度下储存，来制备制剂。Asn-六肽损失是单指数的，并在剩余约30％时达到平稳状态。肽及其已知的脱酰胺产物的总回收率约为肽负载量的30％。具有荧光检测的尺寸排阻色谱法表明在6 M盐酸胍存在下稳定的PVP肽加合物的形成。使用N-乙酰基苯丙氨酸，苯丙氨酸乙酯和N-乙酰基酪氨酸乙酯进行的相似稳定性研究表明，该反应涉及N末端肽。在羧肽酶-A的存在下，加合物被破坏，表明在肽和PVP之间形成了酰胺键。（15）使用（15）N标记的缬氨酸作为肽N端的模型的N固态核磁共振波谱显示（15）N的不同种群，这表明在酰胺键形成之前