BrAc-Ile-Ile-Trp-D-Trp-Leu-Cys | 1026521-72-1

• 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: BrAc-Ile-Ile-Trp-D-Trp-Leu-Cys
• 英文别名: BrAc-Ile-Ile-Trp-D-Trp-Leu-Cys-OH；(2R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[(2-bromoacetyl)amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoic acid
• CAS: 1026521-72-1
• 化学式: C₄₅H₆₁BrN₈O₈S
• 分子量: 953.998
• InChiKey: XXBDCVDYAVOWQL-QYNUCHCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  63
• 可旋转键数：
  24
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  245
• 氢给体数：
  10
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  BrAc-Ile-Ile-Trp-D-Trp-Leu-Cys 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 c[-Ac-Ile-Ile-Trp-D-Trp-Leu-Cys-]OH
  参考文献：
  名称：

  Structure−Activity Studies of Reduced-Size Gonadotropin-Releasing Hormone Agonists Derived from the Sequence of an Endothelin Antagonist

  摘要：

  We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (K-i = 1.9 mu M) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report structure-activity studies of peptide I in respect to its interactions with the GnRH receptor. Our studies suggest that the bioactive conformation of peptide I, recognized by the GnRH receptor, is of a cyclic nature. Thus cyclic analogues of peptide I exhibit higher affinity to the GnRH receptor and increased agonistic potencies as compared to peptide I itself. A linear peptide, ne-Ile-Trp-D-Trp-Leu-Asp, which presumably forms a similar cyclic conformation, was also shown to be a GnRH agonist. Intraperitoneal administration of Ac-Ile-Ile-Trp-D-Trp-Leu-Cys-OH (K-i = 0.32 mu M), one of the cyclic hexapeptides that we have synthesized, to rats induces secretion of luteinizing hormone (LH) with a potency which is only 1 order of magnitude less than that of GnRH itself. Moreover, plasma levels of LH remained elevated for a longer period of time following the administration of the cyclic hexapeptide. This novel class of GnRH agonists may prove useful in the development of new therapeutics.

  DOI：

  10.1021/jm990432o
• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 Fmoc-S-三苯甲基-L-半胱氨酸 、 溴乙酸 N-羟基琥珀酰亚胺酯 、 Fmoc-D-色氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成 BrAc-Ile-Ile-Trp-D-Trp-Leu-Cys
  参考文献：
  名称：

  Structure−Activity Studies of Reduced-Size Gonadotropin-Releasing Hormone Agonists Derived from the Sequence of an Endothelin Antagonist

  摘要：

  We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (K-i = 1.9 mu M) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report structure-activity studies of peptide I in respect to its interactions with the GnRH receptor. Our studies suggest that the bioactive conformation of peptide I, recognized by the GnRH receptor, is of a cyclic nature. Thus cyclic analogues of peptide I exhibit higher affinity to the GnRH receptor and increased agonistic potencies as compared to peptide I itself. A linear peptide, ne-Ile-Trp-D-Trp-Leu-Asp, which presumably forms a similar cyclic conformation, was also shown to be a GnRH agonist. Intraperitoneal administration of Ac-Ile-Ile-Trp-D-Trp-Leu-Cys-OH (K-i = 0.32 mu M), one of the cyclic hexapeptides that we have synthesized, to rats induces secretion of luteinizing hormone (LH) with a potency which is only 1 order of magnitude less than that of GnRH itself. Moreover, plasma levels of LH remained elevated for a longer period of time following the administration of the cyclic hexapeptide. This novel class of GnRH agonists may prove useful in the development of new therapeutics.

  DOI：

  10.1021/jm990432o

文献信息

• Structure−Activity Studies of Reduced-Size Gonadotropin-Releasing Hormone Agonists Derived from the Sequence of an Endothelin Antagonist
  作者：Dror Yahalom、Shai Rahimipour、Yitzhak Koch、Nurit Ben-Aroya、Mati Fridkin

  DOI：10.1021/jm990432o

  日期：2000.7.1

  We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (K-i = 1.9 mu M) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report structure-activity studies of peptide I in respect to its interactions with the GnRH receptor. Our studies suggest that the bioactive conformation of peptide I, recognized by the GnRH receptor, is of a cyclic nature. Thus cyclic analogues of peptide I exhibit higher affinity to the GnRH receptor and increased agonistic potencies as compared to peptide I itself. A linear peptide, ne-Ile-Trp-D-Trp-Leu-Asp, which presumably forms a similar cyclic conformation, was also shown to be a GnRH agonist. Intraperitoneal administration of Ac-Ile-Ile-Trp-D-Trp-Leu-Cys-OH (K-i = 0.32 mu M), one of the cyclic hexapeptides that we have synthesized, to rats induces secretion of luteinizing hormone (LH) with a potency which is only 1 order of magnitude less than that of GnRH itself. Moreover, plasma levels of LH remained elevated for a longer period of time following the administration of the cyclic hexapeptide. This novel class of GnRH agonists may prove useful in the development of new therapeutics.