N²-2,N⁶-bis<1-imino-2-(α-D-mannopyranosylthio)ethyl>-L-lysyl>-N⁶-<1-imino-2-(α-D-mannopyranosylthio)ethyl>-L-lysine | 79374-11-1

• 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: N²-2,N⁶-bis<1-imino-2-(α-D-mannopyranosylthio)ethyl>-L-lysyl>-N⁶-<1-imino-2-(α-D-mannopyranosylthio)ethyl>-L-lysine
• 英文别名: N2-{N2,N6-bis[1-imino-2-(α-D-mannopyranosylthio)-ethyl]-L-lysyl}-N6-[1-imino-2-(α-D-mannopyranosylthio)ethyl]-L-lysine；N2-{N2,N6-Bis[1-imino-2-(α-D-mannopyranosylthio)ethyl]-L-lysyl}-N6-[1-imino-2-(α-D-mannopyranosylthio)ethyl]-L-lysine；N²-[N²,N⁶-bis[1-imino-2-(α-D-mannopyranosylthio)ethyl]-L-lysyl]-N⁶-[1-imino-2-(α-D-mannopyranosylthio)ethyl]-L-lysine；(2S)-6-[[1-amino-2-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]sulfanylethylidene]amino]-2-[[(2S)-2,6-bis[[1-amino-2-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]sulfanylethylidene]amino]hexanoyl]amino]hexanoic acid
• CAS: 79374-11-1
• 化学式: C₃₆H₆₅N₇O₁₈S₃
• 分子量: 980.146
• InChiKey: GETYPCLVRVSVAL-GZYMBUKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.7
• 重原子数：
  64
• 可旋转键数：
  26
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  528
• 氢给体数：
  17
• 氢受体数：
  24

反应信息

• 作为产物：
  描述：

  cyanomethyl 2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyranoside 在 硼酸三钠 、 sodium methylate 作用下， 反应 24.0h， 生成 N²-2,N⁶-bis<1-imino-2-(α-D-mannopyranosylthio)ethyl>-L-lysyl>-N⁶-<1-imino-2-(α-D-mannopyranosylthio)ethyl>-L-lysine
  参考文献：
  名称：

  Cell-specific ligands for selective drug delivery to tissues and organs

  摘要：

  Various numbers of D-mannose residues have been attached via spacer arms to lysine, dilysine, and oligolysine backbones. These D-mannosyl peptide analogues were found to be potent competitive inhibitors of the uptake of 125I-labeled D-mannose-bovine serum albumin conjugate by rat alveolar macrophages. The inhibitory potency of these synthetic ligands increased with increasing number of carbohydrate moieties. The chirality of the peptide backbone did not appear to play a major role in binding, whereas variations of the length and linkage of the spacer arm notably affected the inhibitory activities. The saccharide specificity of the macrophage receptor was demonstrated by the inactivity of the corresponding D-galactosyl peptide analogues. The L-fucosyl peptide derivative was only weakly active. The trimannosyldilysine ligand (KI = 3.9 microM) and its analogues are potentially useful in selective delivery of therapeutic agents to macrophages.

  DOI：

  10.1021/jm00144a004

文献信息

• Cell-specific glycopeptide ligands
  申请人：Merck & Co., Inc.

  公开号：US04386026A1

  公开（公告）日：1983-05-31

  Cell-specific ligands comprising conjugates of saccharides and amino acids or peptides are synthesized from amino acids such as ornithine, lysine, peptides such as dilysine, diornithine or oligolysine and selected saccharides having reactive functional groups protected by appropriate blocking groups. Such glycopeptides are useful as tissue specific substances, which when coupled with bioactive materials through metabolizable or hydrolyzable linkages, deliver such bioactive materials to the selected site. In this manner, antiinflammatory drugs such as dexamethasone are linked through a metabolizable or hydrolyzable linkage and on administration to an animal suffering from inflammatory disease carries the drug to the site of inflammation for intracellular release. Other examples include the macrophage ligand N.sup.2 -N.sup.2, N.sup.6 -Bis-[3-(.alpha.-D-mannopyranosylthio)propionyl]-6-lysyl-N.sup.6 -[3-(.alpha.-D-mannopyranosylthio)propionyl]-L-lysine, 5, which when coupled to .beta.-glucocerebrosidase, can deliver the enzyme selectively to kupffer cells. This is useful in the enzyme replacement therapy of Gaucher's disease.

  由氨基酸（如鸟氨酸、赖氨酸）、肽（如二赖氨酸、二鸟氨酸或寡赖氨酸）和选定的具有适当阻断基保护的反应性官能团的糖组成的细胞特异性配体，可合成成糖肽。这些糖肽可作为组织特异性物质，通过可代谢或可水解的连接与生物活性材料结合，将这些生物活性材料传递到选择的部位。通过这种方式，如地塞米松等抗炎药物可通过可代谢或可水解的连接结合，并在给患有炎症性疾病的动物施用后将药物携带到炎症部位进行细胞内释放。其他例子包括巨噬细胞配体N.sup.2-N.sup.2，N.sup.6-Bis-[3-(.alpha.-D-甘露糖硫基)丙酰基]-6-赖氨酸-N.sup.6-[3-(.alpha.-D-甘露糖硫基)丙酰基]-L-赖氨酸，5，当它与β-葡糖苷酶结合时，可将酶有选择地传递到库普弗细胞。这对于高氏病的酶替代疗法非常有用。
• Cell-specific ligands for selective drug delivery to tissues and organs
  作者：Mitree M. Ponpipom、Robert L. Bugianesi、James C. Robbins、T. W. Doebber、T. Y. Shen

  DOI：10.1021/jm00144a004

  日期：1981.12

  Various numbers of D-mannose residues have been attached via spacer arms to lysine, dilysine, and oligolysine backbones. These D-mannosyl peptide analogues were found to be potent competitive inhibitors of the uptake of 125I-labeled D-mannose-bovine serum albumin conjugate by rat alveolar macrophages. The inhibitory potency of these synthetic ligands increased with increasing number of carbohydrate moieties. The chirality of the peptide backbone did not appear to play a major role in binding, whereas variations of the length and linkage of the spacer arm notably affected the inhibitory activities. The saccharide specificity of the macrophage receptor was demonstrated by the inactivity of the corresponding D-galactosyl peptide analogues. The L-fucosyl peptide derivative was only weakly active. The trimannosyldilysine ligand (KI = 3.9 microM) and its analogues are potentially useful in selective delivery of therapeutic agents to macrophages.