succinyl bis | 102817-61-8

• 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: succinyl bis
• 英文别名: N,N'-succinyl-bis-glycine；N,N'-Succinyl-bis-glycin；Succinyl-bis-aminoessigsaeure；Succinyldiglycin；Glycine, N,N'-(1,4-dioxo-1,4-butanediyl)bis-；2-[[4-(carboxymethylamino)-4-oxobutanoyl]amino]acetic acid
• CAS: 102817-61-8
• 化学式: C₈H₁₂N₂O₆
• 分子量: 232.193
• InChiKey: LUYWFGWEDPEJNS-UHFFFAOYSA-N

物化性质

• 熔点：
  205 °C(Solv: ethanol (64-17-5))
• 沸点：
  742.9±55.0 °C(Predicted)
• 密度：
  1.435±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  succinyl bis 在 钯 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 succinyl bis
  参考文献：
  名称：

  Optimum Cross-linking Spacer Length of Dimeric Neurokinin B Analogs for Interaction with NK-1 Tachykinin Receptors.

  摘要：

  为寻找与速激肽受体二价相互作用的最佳连接间隔长度，合成了一系列神经激肽B（NKB）羧基端七肽的二聚体类似物。通过琥珀酰双[甘氨酸（n）—OH]在七肽的氨基端进行二聚化，其中甘氨酸的数目从0到4变化。二聚体D–（甘氨酸）n–NKB4—10，即琥珀酰双[甘氨酸（n）–天冬氨酸–丝氨酸–苯丙氨酸–缬氨酸–甘氨酸–亮氨酸–蛋氨酸–NH2]（n = 0—4），在利用大鼠输精管进行的实验中几乎无活性，表明它们与NK-2受体亚型无相互作用。相比之下，这些二聚体在含有所有NK-1、NK-2和NK-3受体的大鼠回肠（GPI）中非常活跃。当连接间隔为n = 2的寡甘氨酸时，相对活性最高，而链长更短和更长的二聚体（n = 0和1；3和4）活性显著降低。为了明确二聚体在GPI中结合的受体亚型（NK-1或NK-3），在NK-1受体被甲酯化的P物质脱敏的条件下检测了二聚体。所有二聚体的收缩活性都急剧降低，表明二聚体专门与NK-1受体相互作用。进一步通过利用阿托品阻断NK-3受体的反应，证实了这一点，阿托品对二聚体的收缩活性没有影响。结果表明，二聚体通过桥接相邻的两个结合位点与NK-1受体发生二价相互作用。

  DOI：

  10.1246/bcsj.66.196
• 作为产物：
  描述：

  di-tert-butyl 2,2'-(succinylbisglycine) 在 三乙基硅烷 、 三氟乙酸 作用下， 生成 succinyl bis
  参考文献：
  名称：

  Mimicry of High-Density Lipoprotein: Functional Peptide–Lipid Nanoparticles Based on Multivalent Peptide Constructs

  摘要：

  We describe an approach for engineering peptide lipid nanoparticles that function similarly to high-density lipoprotein (HDL). Branched, multivalent constructs, bearing multiple 23- or 16-amino-acid peptides, were designed, synthesized, and combined with phospholipids to produce nanometer-scale discoidal HDL-like particles. A variety of biophysical techniques were employed to characterize the constructs, including size exclusion chromatography, analytical ultracentrifuge sedimentation, circular dichroism, transmission electron microscopy, and fluorescence spectroscopy. The nanoparticles functioned in vitro (human and mouse plasma) and in vivo (mice) to rapidly remodel large native HDLs into small lipid-poor HDL particles, which are key acceptors of cholesterol in reverse cholesterol transport. Fluorescent labeling studies showed that the constituents of the nanoparticles readily distributed into native HDLs, such that the peptide constructs coexisted with apolipoprotein A-I (apoA-I), the main structural protein in HDLs. Importantly, nanolipid particles containing multivalent peptides promoted efficient. cellular cholesterol efflux and were functionally superior to those derived from monomeric apoA-I mimetic peptides. The multivalent peptide lipid nanoparticles were also remarkably stable toward enzymatic digestion in vitro and displayed long half-lives and desirable pharmacokinetic profiles in mice, providing a real practical advantage over previously studied linear or tandem helical peptides. Encouragingly, a two-week exploratory efficacy study in a widely used animal model for atherosclerosis research (LDLr-null mice) using nanoparticles constructed from a trimeric peptide demonstrated an exceptional 50% reduction in the plasma total cholesterol levels compared to the control group. Altogether, the studies reported here point to an attractive avenue for designing synthetic, HDL-like nanoparticles, with potential for treating atherosclerosis.

  DOI：

  10.1021/ja404714a

文献信息

• Opioid agonist and antagonist bivalent ligands. The relationship between spacer length and selectivity at multiple opioid receptors
  作者：P. S. Portoghese、D. L. Larson、L. M. Sayre、C. B. Yim、G. Ronsisvalle、S. W. Tam、A. E. Takemori

  DOI：10.1021/jm00160a010

  日期：1986.10

  mu receptors as a function of spacer length. Also, delta receptor selectivity increased as the spacer was lengthened. The naltrexamine bivalent ligands (9-13) effectively antagonized the mu receptor agonist morphine in the GPI at the same optimal spacer length (n = 2) as in the agonist series. However, the peak antagonism of ethylketazocine, a kappa receptor agonist, occurred with the bivalent ligand

  合成了含有与不同长度的间隔基连接的羟吗啡胺或纳曲胺药效团的二价配体，并评估了它们在mu，κ和δ阿片样受体上的选择性。羟吗啡胺二价配体（1-8）在电刺激的豚鼠回肠纵向肌肉制剂（GPI）上起mu激动剂的作用。在这些系列中，赋予峰值激动剂活性的间隔基总共包含四个甘氨酰单元（n = 2）。对豚鼠脑膜的结合研究表明，在mu受体处，定性相似的谱是间隔子长度的函数。同样，随着间隔物的延长，δ受体选择性也增加。纳曲胺二价配体（9-13）以与激动剂系列相同的最佳间隔区长度（n = 2）有效拮抗GPI中的mu受体激动剂吗啡。然而，κ酮受体激动剂乙基酮唑嗪的峰值拮抗作用发生在含有最短间隔基（n = 0）的二价配体9上，发现9是该系列中选择性最高的κ拮抗剂。虽然受体结合在GPI中与kappa拮抗剂的活性大致相似，但在μ阿片受体上未观察到结合与拮抗剂活性之间的相关性。讨论了这些结果的可能意义。在μ阿片受体上未观察到
• Synthesis and antistaphylococcic activity of dicarboxylic acid derivatives having an amino acid fragment
  作者：N. A. Grigoryan、Z. O. Mndzhoyan、É. V. Kazaryan、Yu. Z. Ter-Zakharyan、O. L. Mndzhoyan

  DOI：10.1007/bf00766456

  日期：1992.2
• Curtius, Journal fur praktische Chemie (Leipzig 1954), 1915, vol. <2> 91, p. 23
  作者：Curtius

  DOI：——

  日期：——
• Optimum Cross-linking Spacer Length of Dimeric Neurokinin B Analogs for Interaction with NK-1 Tachykinin Receptors.
  作者：Hiroshi Matsumoto、Yasuyuki Shimohigashi、Yukio Takano、Kazuyasu Sakaguchi、Hiro-o Kamiya、Motonori Ohno

  DOI：10.1246/bcsj.66.196

  日期：——

  A series of dimeric analogs of neurokinin B (NKB) COOH-terminal heptapeptide were synthesized in order to find an optimum length of cross-linking spacer for bivalent interaction with tachykinin receptors. Dimerization was carried out at the NH2-terminus of heptapeptide with succinyl bis[(Gly)n–OH], in which the number of glycine varies from 0 to 4. Dimers D–(Gly)n–NKB4—10, namely succinyl bis[(Gly)n–Asp–Ser–Phe–Val–Gly–Leu–Met–NH2] (n = 0—4), were almost inactive in the assay using rat vas deferens, indicating that they have no interaction with NK-2 receptor subtype. In contrast, these dimers were very active in guinea pig ileum (GPI) containing all of NK-1, 2, and 3 receptors. Relative activity was highest when the cross-linking spacer with oligoglycine of n = 2, and decreased sharply for dimers with shorter and longer chain lengths (n = 0 and 1; 3 and 4). In order to specify receptor subtype (NK-1 or NK-3) in GPI to which dimers bind, dimers were examined under the conditions that NK-1 receptors are desensitized by substance P methyl ester. All dimers exhibited drastically diminished contractile activity, indicating that dimers exclusively interact with NK-1. This was further confirmed by blocking the response of NK-3 receptors with atropine, which had no effect on the contractile activity of dimers. The results suggested that dimers interact bivalently with NK-1 receptors by bridging adjacent two binding sites.

  为寻找与速激肽受体二价相互作用的最佳连接间隔长度，合成了一系列神经激肽B（NKB）羧基端七肽的二聚体类似物。通过琥珀酰双[甘氨酸（n）—OH]在七肽的氨基端进行二聚化，其中甘氨酸的数目从0到4变化。二聚体D–（甘氨酸）n–NKB4—10，即琥珀酰双[甘氨酸（n）–天冬氨酸–丝氨酸–苯丙氨酸–缬氨酸–甘氨酸–亮氨酸–蛋氨酸–NH2]（n = 0—4），在利用大鼠输精管进行的实验中几乎无活性，表明它们与NK-2受体亚型无相互作用。相比之下，这些二聚体在含有所有NK-1、NK-2和NK-3受体的大鼠回肠（GPI）中非常活跃。当连接间隔为n = 2的寡甘氨酸时，相对活性最高，而链长更短和更长的二聚体（n = 0和1；3和4）活性显著降低。为了明确二聚体在GPI中结合的受体亚型（NK-1或NK-3），在NK-1受体被甲酯化的P物质脱敏的条件下检测了二聚体。所有二聚体的收缩活性都急剧降低，表明二聚体专门与NK-1受体相互作用。进一步通过利用阿托品阻断NK-3受体的反应，证实了这一点，阿托品对二聚体的收缩活性没有影响。结果表明，二聚体通过桥接相邻的两个结合位点与NK-1受体发生二价相互作用。
• Mimicry of High-Density Lipoprotein: Functional Peptide–Lipid Nanoparticles Based on Multivalent Peptide Constructs
  作者：Yannan Zhao、Tomohiro Imura、Luke J. Leman、Linda K. Curtiss、Bruce E. Maryanoff、M. Reza Ghadiri

  DOI：10.1021/ja404714a

  日期：2013.9.11

  We describe an approach for engineering peptide lipid nanoparticles that function similarly to high-density lipoprotein (HDL). Branched, multivalent constructs, bearing multiple 23- or 16-amino-acid peptides, were designed, synthesized, and combined with phospholipids to produce nanometer-scale discoidal HDL-like particles. A variety of biophysical techniques were employed to characterize the constructs, including size exclusion chromatography, analytical ultracentrifuge sedimentation, circular dichroism, transmission electron microscopy, and fluorescence spectroscopy. The nanoparticles functioned in vitro (human and mouse plasma) and in vivo (mice) to rapidly remodel large native HDLs into small lipid-poor HDL particles, which are key acceptors of cholesterol in reverse cholesterol transport. Fluorescent labeling studies showed that the constituents of the nanoparticles readily distributed into native HDLs, such that the peptide constructs coexisted with apolipoprotein A-I (apoA-I), the main structural protein in HDLs. Importantly, nanolipid particles containing multivalent peptides promoted efficient. cellular cholesterol efflux and were functionally superior to those derived from monomeric apoA-I mimetic peptides. The multivalent peptide lipid nanoparticles were also remarkably stable toward enzymatic digestion in vitro and displayed long half-lives and desirable pharmacokinetic profiles in mice, providing a real practical advantage over previously studied linear or tandem helical peptides. Encouragingly, a two-week exploratory efficacy study in a widely used animal model for atherosclerosis research (LDLr-null mice) using nanoparticles constructed from a trimeric peptide demonstrated an exceptional 50% reduction in the plasma total cholesterol levels compared to the control group. Altogether, the studies reported here point to an attractive avenue for designing synthetic, HDL-like nanoparticles, with potential for treating atherosclerosis.