N^α-(benzyloxycarbonyl)-N^ε-(benzoyl)-L-lysine | 119121-57-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N^α-(benzyloxycarbonyl)-N^ε-(benzoyl)-L-lysine
• 英文别名: ε-B-α-Z-Lys；N^ε-benzoyl-N^α-benzyloxycarbonyl-L-lysine；N^ε-Benzoyl-N^α-benzyloxycarbonyl-L-lysin；(2S)-6-benzamido-2-(phenylmethoxycarbonylamino)hexanoic acid
• CAS: 119121-57-2
• 化学式: C₂₁H₂₄N₂O₅
• 分子量: 384.432
• InChiKey: NLHZTQLTEREAKD-SFHVURJKSA-N

物化性质

• 沸点：
  676.7±55.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  104.73
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N^α-(benzyloxycarbonyl)-N^ε-(benzoyl)-L-lysine 在 五氯化磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以64%的产率得到4-(4-benzoylaminobutyl)oxazolidine-2,5-dione
  参考文献：
  名称：

  Abeysekera, Ajit M.; Grimshaw, James; Perera, Sarath D., Journal of the Chemical Society. Perkin transactions II, 1989, p. 43 - 52

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(苯甲酸基)丁二酰亚胺 、 N-alpha-Cbz-L-赖氨酸 在 borate buffer 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 N^α-(benzyloxycarbonyl)-N^ε-(benzoyl)-L-lysine
  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

文献信息

• Bergmann et al., Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1934, vol. 224, p. 33,35
  作者：Bergmann et al.

  DOI：——

  日期：——
• [EN] METHOD FOR INDUCING ENVIRONMENTAL STRESS TOLERANCE IN PLANTS<br/>[FR] PROCÉDÉ POUR INDUIRE UNE TOLÉRANCE AU STRESS ENVIRONNEMENTAL CHEZ DES PLANTES<br/>[JA] 植物の環境ストレス耐性を誘導する方法
  申请人：AJINOMOTO KK

  公开号：WO2021256546A1

  公开（公告）日：2021-12-23

  植物の環境ストレス耐性を誘導する技術を提供する。アブシジン酸様物質（アブシジン酸やそのアゴニスト等）と含窒素化合物（アミノ酸やアミノ酸誘導体等）を併用することにより植物の環境ストレス耐性を誘導する。