L-亮氨酰甘氨酰甘氨酸 | 1187-50-4

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 甘氨酸类衍生物
• 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: L-亮氨酰甘氨酰甘氨酸
• 中文别名: L-白氨酰甘氨酰甘氨酸
• 英文名称: L-Leu-Gly-Gly
• 英文别名: Leu-Gly-Gly；2-[[2-[[(2S)-2-azaniumyl-4-methylpentanoyl]amino]acetyl]amino]acetate
• CAS: 1187-50-4
• 化学式: C₁₀H₁₉N₃O₄
• mdl: MFCD00065942
• 分子量: 245.279
• InChiKey: VWHGTYCRDRBSFI-ZETCQYMHSA-N

物化性质

• 熔点：
  ~220 °C (dec.)
• 沸点：
  573.7±45.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 海关编码：
  2924199090

反应信息

• 作为反应物：
  描述：

  L-亮氨酰甘氨酰甘氨酸 在 氯化亚砜 、 TEA 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 生成 naproxen-Leu-Gly-Gly-OEt
  参考文献：
  名称：

  Low-molecular-weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates

  摘要：

  Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)alpha-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecule between the drug and the protein further increased the extent and rate of drug release, indicating increased accessability of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes. This has profound implications for the synthesis of suitable conjugates, since the nature of the drug itself, the type of bond, and also spacer length largely determine whether release of the parent drug will occur. Tailor-made spacers containing the correct mode of attachment and the right spacer length are required for this option. Chemical hydrolysis, using acid-sensitive linkers, is suggested as a viable alternative approach.

  DOI：

  10.1021/jm00085a012
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 钯 、 溶剂黄146 作用下， 生成 L-亮氨酰甘氨酰甘氨酸
  参考文献：
  名称：

  Grassmann; Wuensch, Chemische Berichte, 1958, vol. 91, p. 449,453

  摘要：

  DOI：

文献信息

• Inhibition of iodine-125 labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships
  作者：Ki-Hwan Kim、Yvonne Martin、Ellen Otis、James Mao

  DOI：10.1021/jm00121a018

  日期：1989.1

  Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of

  已开发了N-Ac氨基酸，N-Ac二肽和N-Ac三肽在抑制125I标记的瑞氏菌素与黄褐微球菌细胞壁结合中的定量构效关系（QSAR），以探索ristocetin之间的结合细节和N-乙酰化的肽 相关方程表明（1）对于C末端氨基酸侧链具有较大摩尔折射率（MR）值的肽，其结合作用更强；（2）对于极性肽，其结合作用较弱。 （3）N-Ac二肽中的N末端氨基酸对结合亲和力的贡献是C末端氨基酸的12倍，
• Linear energy correlations and failures in the low-energy tandem mass spectra of protonatedN-benzoylated tripeptides: Tools for probing mechanisms of CAD processes
  作者：Daniel G. Morgan、Maurice M. Bursey

  DOI：10.1002/jms.1190300410

  日期：1995.4

  The backbone cleavages for three series of protonated N-benzoyl tripeptide ions were studied in a hybrid tandem mass spectrometer: (i) benzoyl-Gly-Gly-Xxx, where Xxx = Gly, Ala, Val, Leu, Ile, Phe, Tyr, Met, Glu, Pro and Trp, (ii) benzoyl-Gly-Xxx-Gly, where Xxx = Gly, Ala, Leu, Phe, Tyr, Met and Trp, and (iii) benzoyl-Xxx-Gly-Gly, where Xxx = Gly, Ala, Val, Leu, Ile, Phe, Tyr, Met, Pro and Trp. C-Terminal y-type ions and N-terminal a- and b-type ions were noted in all three cases. For benzoyl-Gly-Gly-Xxx, a linear relationship between log (y1/b2) and the proton affinity of the C-terminal amino acid substituents was found: as the proton affinity of the C-terminal residue increases, the fraction of y1 ion formation increases. A similar relationship was noted for the benzoyl-Xxx-Gly-Gly tripeptides between log (y2/b1) and the proton affinity of the N-terminal amino acid substituent: as the proton affinity of the N-terminal residue increases, the fraction of b1 ion formation increases. For the series benzoyl-Gly-Xxx-Gly, these relationships did not hold true. These observations point to similar reaction pathways throughout the benzoyl-Gly-Gly-Xxx series and also similar pathways throughout the benzoyl-Xxx-Gly-Gly, but pathways that are substituent dependent for benzoyl-Gly-Xxx-Gly. The increased correlation coefficients for benzoyl-Gly-Gly-Xxx and benzoyl-Xxx-Gly-Gly when compared with the free tripeptides, suggest that fewer interfering competitive reactions exist, as fewer possibilities for internal hydrogen bonding exist in the N-benzoyl derivatives versus the free compounds.

  在一台混合串联质谱仪上，研究了三种系列的质子化N-苯甲酰三肽离子的骨架断裂：（i）苯甲酰-Gly-Gly-Xxx，其中Xxx = Gly、Ala、Val、Leu、Ile、Phe、Tyr、Met、Glu、Pro和Trp，（ii）苯甲酰-Gly-Xxx-Gly，其中Xxx = Gly、Ala、Leu、Phe、Tyr、Met和Trp，以及（iii）苯甲酰-Xxx-Gly-Gly，其中Xxx = Gly、Ala、Val、Leu、Ile、Phe、Tyr、Met、Pro和Trp。在所有三种情况下，都观察到了C端y型离子和N端a型及b型离子。对于苯甲酰-Gly-Gly-Xxx，发现log（y1/b2）与C端氨基酸取代基的质子亲和力之间存在线性关系：随着C端残基的质子亲和力增加，y1离子的形成分数增加。对于苯甲酰-Xxx-Gly-Gly三肽，log（y2/b1）与N端氨基酸取代基的质子亲和力之间存在类似的关系：随着N端残基的质子亲和力增加，b1离子的形成分数增加。对于苯甲酰-Gly-Xxx-Gly系列，这些关系并不成立。这些观察结果表明，在苯甲酰-Gly-Gly-Xxx系列和苯甲酰-Xxx-Gly-Gly系列中存在类似的反应途径，但对于苯甲酰-Gly-Xxx-Gly，途径依赖于取代基。与自由三肽相比，苯甲酰-Gly-Gly-Xxx和苯甲酰-Xxx-Gly-Gly的相关系数增加，表明存在的干扰竞争反应较少，因为在N-苯甲酰衍生物中内部氢键的可能性比自由化合物少。
• [EN] N-ALKYLATED AMINO ACIDS AND OLIGOPEPTIDES, USES THEREOF AND METHODS FOR PROVIDING THEM.<br/>[FR] ACIDES AMINÉS N-ALKYLÉS ET OLIGOPEPTIDES, LEURS UTILISATIONS ET LEURS PROCÉDÉS DE PRODUCTION
  申请人：UNIV GRONINGEN

  公开号：WO2018178397A1

  公开（公告）日：2018-10-04

  The invention relates to the synthesis of amphiphilic amino acid derivatives, in particular to a method for the N-alkylation of an unprotected amino acid or the N-terminus of an oligopeptide substrate, comprising reacting said unprotected amino acid or oligopeptide substrate with an alcohol, e.g. a fatty alcohol, in the presence of a homogeneous transition metal catalyst.

  该发明涉及两性氨基酸衍生物的合成，特别涉及一种用于对未保护的氨基酸或寡肽底物的N-烷基化的方法，包括将所述未保护的氨基酸或寡肽底物与醇（例如脂肪醇）在均相过渡金属催化剂的存在下反应。
• Potential<scp>d,l</scp>-Amino Acid Sequence Analysis of Peptides from the C-Terminus
  作者：Hiroshi Ohrui、Eigo Itoh、Yoshihiro Nishida、Hiroko Horie、Hiroshi Meguro

  DOI：10.1271/bbb.61.392

  日期：1997.1

  A model tripeptide, Gly-L-Leu-L-Phe, was immobilized with activated aminomethyl polystyrene, and its C-terminal was reduced to an alcohol. This peptidyl alcohol was selectively hydrolyzed at the C-terminal amide bond to afford a polymer-supported dipeptide (Gly-L-Leu) and amino alcohol (Phe-OH). The amino alcohol, including its absolute configuration, was determined by labelling with (+)-MNB-COOH, and the dipeptide was reused for a determination of its C-terminal amino acids. The d, l-amino acids of the tripeptide were sequentially determined from the C-terminus.

  一种模型三肽Gly-L-Leu-L-Phe与活化的氨基甲基聚苯乙烯结合，且其C端被还原为醇。该肽醇在C端酰胺键上选择性水解，生成了聚合物支持的二肽（Gly-L-Leu）和氨基醇（Phe-OH）。通过用（+）-MNB-COOH标记，确定了氨基醇及其绝对构型，并对二肽进行了再利用以确定其C端氨基酸。三肽的d、l-氨基酸从C端依次被确定。
• Synthesis of tripeptide derivatized cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes
  作者：Qaisar Nadeem、Daniel Can、Yunjun Shen、Michael Felber、Zaid Mahmood、Roger Alberto

  DOI：10.1039/c3ob41866a

  日期：——

  We describe the syntheses of half-sandwich complexes of the type [(η5-Cp(CONH-R))M(CO)3] with M = Re or 99mTc. The R group represents different tri-peptides (tpe) which display high binding affinities for oligopeptide transporters PEPT2. The 99mTc complexes were prepared directly from [99mTc(OH2)3(CO)3]+ and Diels–Alder dimerized, cyclopentadienyl derivatized peptides in water. This approach corroborates the feasibility of metal-mediated retro Diels–Alder reactions for the preparation of not only small molecules but also peptides carrying a [(η5-Cp)99mTc(CO)3] tag. We synthesized the Diels–Alder product [(HCpCONH-tpe)2] from Thiele's acid [(η5-HCpCOOH)2] via double peptide coupling. The Re-complexes [(η5-CpCONH-tpe)Re(CO)3] were obtained by attaching [(Cp-COOH)Re(CO)3] directly to the N-terminus of peptides as received from SPPS. The authenticity of the 99mTc-complexes is confirmed by chromatographic comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.

  我们描述了[(η5-Cp(CONH-R))M(CO)3]型半三明治复合物的合成，其中M = Re或99mTc。R基团代表不同的三肽（tpe），它们对寡肽转运蛋白PEPT2具有高结合亲和力。99mTc复合物直接由[99mTc(OH2)3(CO)3]+和Diels-Alder二聚体、环戊二烯衍生物肽在水中制备。这种方法证实了金属介导的反式Diels-Alder反应不仅可用于制备小分子，还可用于制备带有[(η5-Cp)99mTc(CO)3]标签的肽。我们通过双肽偶联从Thiele酸[(η5-HCpCOOH)2]合成了Diels-Alder产物[(HCpCONH-tpe)2]。通过将[(Cp-COOH)Re(CO)3]直接连接到从SPPS获得的肽的N端，获得了Re复合物[(η5-CpCONH-tpe)Re(CO)3]。通过与相应的铼复合物进行色谱比较，证实了99mTc复合物的真实性，并通过光谱技术对其进行了充分表征。

表征谱图