CF3COOH*H-Tyr-Pro-Ser-NH2 | 78331-14-3

• 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: CF3COOH*H-Tyr-Pro-Ser-NH2
• 英文别名: H-Tyr-Pro-Ser-NH2*CF3COOH
• CAS: 78331-14-3
• 化学式: C₂HF₃O₂*C₁₇H₂₄N₄O₅
• 分子量: 478.425
• InChiKey: DSFSWUJYNZRUBG-JKBZPBJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.15
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  196.28
• 氢给体数：
  6.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Boc-D-Arg(Tos)-Phe-Gly-OH 、 CF3COOH*H-Tyr-Pro-Ser-NH2 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 三乙胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 以92%的产率得到Boc-D-Arg(Tos)-Phe-Gly-Tyr-Pro-Ser-NH2
  参考文献：
  名称：

  Studies on analgesic oligopeptides. IV. Synthesis and analgesic activity of N-terminal shorter analogs of (D-Arg2)dermorphin and des-Tyr1-dermorphin analogs.

  摘要：

  采用传统的溶液法合成了去酪氨酸1-德吗啡、去酪氨酸1-[D-Arg2]德吗啡和[D-Arg2]德吗啡的N-末端二肽、三肽、四肽和六肽酰胺，并通过对小鼠皮下注射后进行尾压试验来检测它们的镇痛活性。N-末端的四肽酰胺 H-Tyr-D-Arg-Phe-Gly-NH2 显示出极强的活性，其摩尔活性是吗啡的 31 倍，而 N-末端的三肽和二肽酰胺即使剂量高达 40 毫克/千克（皮下注射）也没有活性。

  DOI：

  10.1248/cpb.33.4865

文献信息

• Studies on analgesic oligopeptides. III. Synthesis and analgesic activity after subcutaneous administration of (D-Arg2)dermorphin and its N-terminal tetrapeptide analogs.
  作者：YUSUKE SASAKI、MICHIKO MATSUI、HIROKI FUJITA、MASAHIRO HOSONO、MASUMI TAGUCHI、KENJI SUZUKI、SHINOBU SAKURADA、TAKUMI SATO、TSUKASA SAKURADA、KENSUKE KISARA

  DOI：10.1248/cpb.33.1528

  日期：——

  [D-Arg2] dermorphin and nineteen N-terminal tetrapeptide analogs were synthesized by a conventional solution method and their analgesic activities after subcutaneous administration to mice were examined. The analgesic effect was assessed by means of the tail pressure test. [D-Arg2] dermorphin was found to have analgesic potency equal to or slightly greater than that of dermorphin. The N-terminal tetrapeptide, H-Tyr-D-Arg-Phe-Gly-OH (I), showed a potency 4.8 times that of morphine and comparable with that of dermorphin on a molar basis. Among the tetrapeptide analogs, several analogs in which Gly4 was replaced by sarcosine or D-Ala exhibited very potent activity more than that of I. On the other hand, replacement of Gly4 by Pro, Leu or D-Leu resulted in a marked decrease in potency. Replacement of either Phe3 by other aromatic amino acid or D-Arg2 by other basic D-amino acid gave analogs with greatly decreased activities. However, one analog whose guanidino functionality on D-Arg2 was blocked by a nitro group, showed activity one-third that of the parent peptide (I). On the basis of these results, the structure-activity relationship for the tetrapeptide is discussed.

  采用传统的溶液法合成了[D-Arg2] dermorphin 和 19 种 N 末端四肽类似物，并考察了它们在小鼠皮下注射后的镇痛活性。镇痛效果通过尾压试验进行评估。结果发现，[D-Arg2] dermorphin 的镇痛效力等于或略高于 dermorphin。N 端四肽 H-Tyr-D-Arg-Phe-Gly-OH (I)的药效是吗啡的 4.8 倍，按摩尔计与去甲吗啡相当。在四肽类似物中，有几种类似物的 Gly4 被肌氨酸或 D-Ala 取代，其活性非常强，超过了 I。用其他芳香族氨基酸取代 Phe3 或用其他碱性 D-氨基酸取代 D-Arg2，都会使类似物的活性大大降低。不过，有一种类似物的 D-Arg2 上的胍基功能被硝基阻断，其活性只有母肽（I）的三分之一。在这些结果的基础上，讨论了四肽的结构-活性关系。