Fmoc-Ser-Ψ[(E)CH=C]-Pro-OH | 817620-02-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Ser-Ψ[(E)CH=C]-Pro-OH
• 英文别名: (1R,2E)-2-[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-hydroxypropylidene]cyclopentane-1-carboxylic acid
• CAS: 817620-02-3
• 化学式: C₂₄H₂₅NO₅
• 分子量: 407.466
• InChiKey: UUSITZWVTZSBAJ-OMYPGEHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Fmoc-Ser-Ψ[(E)CH=C]-Pro-OH 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 Phosphoric acid mono-{(R)-2-[(S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-3-[(R)-2-((S)-4-amino-1-methylcarbamoyl-butylcarbamoyl)-cyclopent-(E)-ylidene]-propyl} ester
  参考文献：
  名称：

  Conformationally Locked Isostere of PhosphoSer−cis-Pro Inhibits Pin1 23-Fold Better than PhosphoSer−trans-Pro Isostere

  摘要：

  Stereoisomeric cis and trans substrate analogues for Pint were designed and synthesized. The central phosphoSer-Pro core of the Pin1 substrate was replaced by cis and trans amide isosteres in Ac-Phe-Phe-pser-Psi[(Z and E)CH=C]-Pro-Arg-NH2, 1 and 2, peptidomimetics. They were synthesized on solid phase in 17% yield for the cis analogue 1, and 16% yield for the trans analogue 2. A second trans amide isostere with a C-terminal N-methylamide 3 was synthesized in 7% yield. The protease-coupled Pint assay showed that all three compounds inhibited the Pint peptidyl-prolyl isomerase (PPlase) enzymatic activity. The cis isostere 1 was 23 times more potent (K-i = 1.74 +/- 0.08 muM) than its trans counterpart 2 (K-i = 40 +/- 2 muM) in competitive inhibition of Pint. These results suggest that the catalytic site of Pin1 binds cis substrates more tightly in aqueous solution. Antiproliferative activity toward the A2780 human ovarian cancer cell line by the cis and trans analogues correlates with Pint inhibition results.

  DOI：

  10.1021/ja046396m
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 (R)-2-[(R)-2-Amino-3-hydroxy-prop-(E)-ylidene]-cyclopentanecarboxylic acid 在 碳酸氢钠 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以650 mg的产率得到Fmoc-Ser-Ψ[(E)CH=C]-Pro-OH
  参考文献：
  名称：

  Conformationally Locked Isostere of PhosphoSer−cis-Pro Inhibits Pin1 23-Fold Better than PhosphoSer−trans-Pro Isostere

  摘要：

  Stereoisomeric cis and trans substrate analogues for Pint were designed and synthesized. The central phosphoSer-Pro core of the Pin1 substrate was replaced by cis and trans amide isosteres in Ac-Phe-Phe-pser-Psi[(Z and E)CH=C]-Pro-Arg-NH2, 1 and 2, peptidomimetics. They were synthesized on solid phase in 17% yield for the cis analogue 1, and 16% yield for the trans analogue 2. A second trans amide isostere with a C-terminal N-methylamide 3 was synthesized in 7% yield. The protease-coupled Pint assay showed that all three compounds inhibited the Pint peptidyl-prolyl isomerase (PPlase) enzymatic activity. The cis isostere 1 was 23 times more potent (K-i = 1.74 +/- 0.08 muM) than its trans counterpart 2 (K-i = 40 +/- 2 muM) in competitive inhibition of Pint. These results suggest that the catalytic site of Pin1 binds cis substrates more tightly in aqueous solution. Antiproliferative activity toward the A2780 human ovarian cancer cell line by the cis and trans analogues correlates with Pint inhibition results.

  DOI：

  10.1021/ja046396m

文献信息

• Potent activity of a PK/PBAN analog with an (E)-alkene, trans-Pro mimic identifies the Pro orientation and core conformation during interaction with HevPBANR-C receptor
  作者：Ronald J. Nachman、Young-Joon Kim、Xiaodong J. Wang、Felicia A. Etzkorn、Krzysztof Kaczmarek、Janusz Zabrocki、Michael E. Adams

  DOI：10.1016/j.bmc.2009.03.036

  日期：2009.6

  The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a multifunctional role in an array of important physiological processes in insects, including regulation of sex pheromone biosynthesis in moths. A cyclic PK/PBAN analog (cyclo[NTSFTPRL]) retains significant activity on the pheromonotropic HevPBANR receptor from the tobacco budworm Heliothis virescens expressed in CHO-K1 cells. Previous studies indicate that this rigid, cyclic analog adopts a type I beta-turn with a transPro over residues TPRL within the core PK/PBAN region. An analog containing an (E)-alkene, trans-Pro mimetic motif was synthesized, and upon evaluation on the HevPBANR receptor found to have an EC(50) value that is not statistically different from a parent C-terminal PK/PBAN hexapeptide sequence. The results, in aggregate, provide strong evidence for the orientation of Pro and the core conformation of PK/PBAN neuropeptides during interaction with the expressed PBAN receptor. The work further identifies a novel scaffold with which to design mimetic PBAN analogs as potential leads in the development of environmentally favorable pest management agents capable of disrupting PK/PBAN-regulated pheromone signaling systems. Published by Elsevier Ltd.
• Alkene Mimics
  申请人：Etzkorn Felicia A.

  公开号：US20080261923A1

  公开（公告）日：2008-10-23

  Ac-Phe-Tyr-phosphoSer-Ψ[CH═C]-Pro-Arg-NH 2 AND Fmoc-bis(pivaloylmethoxy)phosphoSer-Ψ[CH═C]-Pro-2-aminoethyl-(3-indole); and their Phospho-(D)-serine stereoisomers are novel compounds. Ψ refers to a pseudo amide. Such novel compounds advantageously may be used as alkene mimics.
• Conformationally Locked Isostere of PhosphoSer−<i>cis</i>-Pro Inhibits Pin1 23-Fold Better than PhosphoSer−<i>trans</i>-Pro Isostere
  作者：Xiaodong J. Wang、Bailing Xu、Ashley B. Mullins、Freda K. Neiler、Felicia A. Etzkorn

  DOI：10.1021/ja046396m

  日期：2004.12.1

  Stereoisomeric cis and trans substrate analogues for Pint were designed and synthesized. The central phosphoSer-Pro core of the Pin1 substrate was replaced by cis and trans amide isosteres in Ac-Phe-Phe-pser-Psi[(Z and E)CH=C]-Pro-Arg-NH2, 1 and 2, peptidomimetics. They were synthesized on solid phase in 17% yield for the cis analogue 1, and 16% yield for the trans analogue 2. A second trans amide isostere with a C-terminal N-methylamide 3 was synthesized in 7% yield. The protease-coupled Pint assay showed that all three compounds inhibited the Pint peptidyl-prolyl isomerase (PPlase) enzymatic activity. The cis isostere 1 was 23 times more potent (K-i = 1.74 +/- 0.08 muM) than its trans counterpart 2 (K-i = 40 +/- 2 muM) in competitive inhibition of Pint. These results suggest that the catalytic site of Pin1 binds cis substrates more tightly in aqueous solution. Antiproliferative activity toward the A2780 human ovarian cancer cell line by the cis and trans analogues correlates with Pint inhibition results.