3-O-((鼠李吡喃糖基-(1-3)-吡喃木糖基-(1-2)-)(吡喃葡萄糖基-(1-3))-吡喃葡萄糖基-(1-3)-吡喃葡萄糖基)螺甾烷-2,3-二醇 | 139570-70-0

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: 3-O-((鼠李吡喃糖基-(1-3)-吡喃木糖基-(1-2)-)(吡喃葡萄糖基-(1-3))-吡喃葡萄糖基-(1-3)-吡喃葡萄糖基)螺甾烷-2,3-二醇
• 英文名称: LHRH, lysine(6)-glutaryl-2-(hydroxymethyl)anthraquinone
• 英文别名: (9,10-dioxoanthracen-2-yl)methyl 5-[[(5R)-6-[[(2S)-1-[[(2S)-1-[(2S)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-[[(2S)-2-[[(2S)-3-hydroxy-2-[[(2S)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]amino]-5-oxopentanoate
• CAS: 139570-70-0
• 化学式: C₇₉H₉₈N₁₈O₁₈
• 分子量: 1587.76
• InChiKey: BSKOWQLQBJGVOI-ZCPJTSLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  115
• 可旋转键数：
  44
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  562
• 氢给体数：
  18
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  pGlu-His-Trp-Ser-Tyr-D-Lys-Leu-Arg-Pro-Gly-NH₂ 、 5-[(9,10-二氧代蒽-2-基)甲氧基]-5-氧代戊酸 在 N-甲基吗啉 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以65%的产率得到3-O-((鼠李吡喃糖基-(1-3)-吡喃木糖基-(1-2)-)(吡喃葡萄糖基-(1-3))-吡喃葡萄糖基-(1-3)-吡喃葡萄糖基)螺甾烷-2,3-二醇
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Long-Acting, Potent Analogue of Gonadotropin-Releasing Hormone

  摘要：

  The design, synthesis, and biological evaluation of a gonadotropin-releasing hormone (GnRH) agonist, [D-Lys(6)(1,3,8-trihydroxy-6-carboxyanthraquinone)]GnRH ([D-Lys(6)(Emo)]GnRH), is described. Synthesis of this analogue was carried out in a homogeneous solution as well as on a polymer support. [D-Lys(6)(Emo)]GnRH was found to bind to rat pituitary GnRH receptors (IC50 = 0.25 nM), to induce luteinizing hormone (LH) release (ED50 = 27 pM), and to be devoid of any toxicity. This analogue also proved to be a very potent agonist in vivo and exhibited a prolonged bioactivity. Six hours after its administration to rats, LH levels were substantially higher than those of rats treated with a 10-fold higher dose of the parent peptide. Moreover, chronic treatment of adult male rats with [D-Lys(6)(Emo)]GnRH (0.1 nmol/rat) for one week resulted in a further decrease of the weight of the testes and prostate as compared to those of rats that were treated with a higher dose of [D-Lys] GnRH (1 nmol/rat). The prolonged activity of [D-Lys(6)(Emo)]GnRH may be attributed to its emodic acid moiety, which enhances the binding affinity of the analogue to human serum albumin. Indeed, we found that emodic. acid binds to human serum albumin almost completely at the examined range of concentrations.

  DOI：

  10.1021/jm010112g

文献信息

• Design, Synthesis, and Evaluation of a Long-Acting, Potent Analogue of Gonadotropin-Releasing Hormone
  作者：Shai Rahimipour、Nurit Ben-Aroya、Mati Fridkin、Yitzhak Koch

  DOI：10.1021/jm010112g

  日期：2001.10.1

  The design, synthesis, and biological evaluation of a gonadotropin-releasing hormone (GnRH) agonist, [D-Lys(6)(1,3,8-trihydroxy-6-carboxyanthraquinone)]GnRH ([D-Lys(6)(Emo)]GnRH), is described. Synthesis of this analogue was carried out in a homogeneous solution as well as on a polymer support. [D-Lys(6)(Emo)]GnRH was found to bind to rat pituitary GnRH receptors (IC50 = 0.25 nM), to induce luteinizing hormone (LH) release (ED50 = 27 pM), and to be devoid of any toxicity. This analogue also proved to be a very potent agonist in vivo and exhibited a prolonged bioactivity. Six hours after its administration to rats, LH levels were substantially higher than those of rats treated with a 10-fold higher dose of the parent peptide. Moreover, chronic treatment of adult male rats with [D-Lys(6)(Emo)]GnRH (0.1 nmol/rat) for one week resulted in a further decrease of the weight of the testes and prostate as compared to those of rats that were treated with a higher dose of [D-Lys] GnRH (1 nmol/rat). The prolonged activity of [D-Lys(6)(Emo)]GnRH may be attributed to its emodic acid moiety, which enhances the binding affinity of the analogue to human serum albumin. Indeed, we found that emodic. acid binds to human serum albumin almost completely at the examined range of concentrations.