Fmoc-Ser-Ψ[(Z)CH=C]-Pro-OH | 817619-94-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Ser-Ψ[(Z)CH=C]-Pro-OH
• 英文别名: Fmoc-SerΨ[(Z)CH=C]-Pro-OH；(1R,2Z)-2-[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-hydroxypropylidene]cyclopentane-1-carboxylic acid
• CAS: 817619-94-6
• 化学式: C₂₄H₂₅NO₅
• 分子量: 407.466
• InChiKey: UUSITZWVTZSBAJ-FBCVODPVSA-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[(Z)CH=C]-Pro-OH 在 咪唑 、 叔丁基二甲基氯硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以55%的产率得到
  参考文献：
  名称：

  A phosphorylated prodrug for the inhibition of Pin1

  摘要：

  Fmoc-pSer-psi[(Z)CH = C]-Pro-(2)-N-(3)-ethylaminoindole 1, showed moderate inhibition towards the mitotic regulator, Pin1 (IC50 = 28.3 mu M). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-psi[(Z)CH = C]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC50 = 46.2 mu M) was improved significantly in 2 (IC50 = 26.9 mu M), comparable to the IC50 of 1 towards Pin1 enzymatic activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.073
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 (R)-2-[(R)-2-Amino-3-hydroxy-prop-(Z)-ylidene]-cyclopentanecarboxylic acid 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以77 mg的产率得到Fmoc-Ser-Ψ[(Z)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

• [EN] ALKENE MIMICS<br/>[FR] ANALOGUES D'ALCENES
  申请人：VIRGINIA TECH INTELL PROP

  公开号：WO2006020417A3

  公开（公告）日：2006-07-13
• 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.
• A phosphorylated prodrug for the inhibition of Pin1
  作者：Song Zhao、Felicia A. Etzkorn

  DOI：10.1016/j.bmcl.2007.09.073

  日期：2007.12

  Fmoc-pSer-psi[(Z)CH = C]-Pro-(2)-N-(3)-ethylaminoindole 1, showed moderate inhibition towards the mitotic regulator, Pin1 (IC50 = 28.3 mu M). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-psi[(Z)CH = C]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC50 = 46.2 mu M) was improved significantly in 2 (IC50 = 26.9 mu M), comparable to the IC50 of 1 towards Pin1 enzymatic activity. (c) 2007 Elsevier Ltd. All rights reserved.