L-Val-L-Tyr-L-Pro-L-Asp-Gly-L-Ala | 93245-71-7

• 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: L-Val-L-Tyr-L-Pro-L-Asp-Gly-L-Ala
• 英文别名: Valyl-tyrosyl-prolyl-isoaspartyl-glycyl-alanine；(3S)-3-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-[[2-[[(1S)-1-carboxyethyl]amino]-2-oxoethyl]amino]-4-oxobutanoic acid
• CAS: 93245-71-7
• 化学式: C₂₈H₄₀N₆O₁₀
• 分子量: 620.66
• InChiKey: SWPINJCGZHYCMT-GJLLLRFJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 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：
  258
• 氢给体数：
  8
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-(3-甲基哌嗪-1-基)吡啶-3-羧酸 在 水 作用下， 反应 2880.0h， 生成 L-Val-L-Tyr-L-Pro-L-cyclic imide-Gly-L-Ala 、 L-Val-L-Tyr-L-Pro-L-Asp-Gly-L-Ala 、 L-Val-L-Tyr-L-Pro-L-isoAsp-Gly-L-Ala
  参考文献：
  名称：

  Chemical stability of peptides in polymers. 2. Discriminating between solvent and plasticizing effects of water on peptide deamidation in poly(vinylpyrrolidone)

  摘要：

  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.

  DOI：

  10.1021/js9802289

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. 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.