2-[(3S,7S,8aR)-7-(9H-fluoren-9-ylmethoxycarbonylamino)-1,4-dioxo-3-(2-oxo-2-prop-2-enoxyethyl)-3,6,7,8-tetrahydro-2H-pyrrolo[1,2-a]pyrazin-8a-yl]acetic acid | 183808-19-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-[(3S,7S,8aR)-7-(9H-fluoren-9-ylmethoxycarbonylamino)-1,4-dioxo-3-(2-oxo-2-prop-2-enoxyethyl)-3,6,7,8-tetrahydro-2H-pyrrolo[1,2-a]pyrazin-8a-yl]acetic acid
• CAS: 183808-19-7
• 化学式: C₂₉H₂₉N₃O₈
• 分子量: 547.565
• InChiKey: ZQWPLZZZYWGPSV-QFBFHCEGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Fmoc-L-丙氨酸 、 Fmoc-L-脯氨酸 、 2-[(3S,7S,8aR)-7-(9H-fluoren-9-ylmethoxycarbonylamino)-1,4-dioxo-3-(2-oxo-2-prop-2-enoxyethyl)-3,6,7,8-tetrahydro-2H-pyrrolo[1,2-a]pyrazin-8a-yl]acetic acid 、 (S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-[(4-methoxy-phenyl)-diphenyl-methyl]-succinamic acid 生成
  参考文献：
  名称：

  Synthesis, Conformational Properties, and Immunogenicity of a Cyclic Template-Bound Peptide Mimetic Containing an NPNA Motif from the Circumsporozoite Protein of Plasmodium falciparum

  摘要：

  The immunodominant central portion of the circumsporozoite (CS) surface protein of the malaria parasite Plasmodium falciparum contains a tetrapeptide motif, Asn-Pro-Asn-Ala (NPNA), tandemly repeated almost 40 times. The three-dimensional structure of the CS protein, including the central repeat region, is presently unknown. We have investigated an approach to stabilize beta-turns in a single NPNA motif, by its incorporation into a template-bound cyclic peptide comprising the sequence ANPNAA. The template was designed to stabilize beta-turns in the peptide loop and to allow its conjugation to T-cell epitopes in a multiple antigen-peptide. NMR studies and MD simulations with time-averaged NOE-derived upper distance restraints support the formation of a stable beta-I turn conformation in the NPNA motif of this template-bound antigen. Balb/c mice immunized with a multiple-antigen-peptide containing four copies of the template-bound loop conjugated to a single universal T-cell epitope produced antibodies that bound P. falciparum sporozoites in immunofluorescence assays. These results provide further support for the immunological relevance of a type-I beta-turn conformation based on the NPNA cadence in the repeat region of the CS protein and illustrate the use of a novel template for the evaluation of conformationally constrained peptide immunogens.

  DOI：

  10.1021/ja980444j
• 作为产物：
  描述：

  L-羟基脯氨酸 在 palladium on activated charcoal 氯化亚砜 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三苯基膦 、 甲基肼 、 三氟乙酸 、 柠檬酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium diisopropyl amide 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 2-[(3S,7S,8aR)-7-(9H-fluoren-9-ylmethoxycarbonylamino)-1,4-dioxo-3-(2-oxo-2-prop-2-enoxyethyl)-3,6,7,8-tetrahydro-2H-pyrrolo[1,2-a]pyrazin-8a-yl]acetic acid
  参考文献：
  名称：

  A template for the solid-phase synthesis of conformationally restricted protein loop mimetics

  摘要：

  三功能模板1由反式-4-羟基-L-脯氨酸和L-天冬氨酸合成，固定在固体载体上，用于固相合成含Asn-Pro-Asn-Ala（NPNA）模序的环状构象限制性六肽模拟物；NMR显示其在水溶液中形成稳定的β-转角构象。

  DOI：

  10.1039/cc9960002155

文献信息

• A template for the solid-phase synthesis of conformationally restricted protein loop mimetics
  作者：Fabienne Emery、Christian Bisang、Michel Favre、Luyong Jiang、John A. Robinson

  DOI：10.1039/cc9960002155

  日期：——

  A trifunctional template 1 is synthesized from trans-4-hydroxy-L-proline and L-aspartic acid, immobilized on a solid-support, and used for the solid-phase synthesis of a cyclic conformationally restrained hexapeptide loop mimetic containing the motif Asn-Pro-Asn-Ala (NPNA); this is shown by NMR to populate a stable β-turn conformation in aqueous solution.

  三功能模板1由反式-4-羟基-L-脯氨酸和L-天冬氨酸合成，固定在固体载体上，用于固相合成含Asn-Pro-Asn-Ala（NPNA）模序的环状构象限制性六肽模拟物；NMR显示其在水溶液中形成稳定的β-转角构象。
• Synthesis, Conformational Properties, and Immunogenicity of a Cyclic Template-Bound Peptide Mimetic Containing an NPNA Motif from the Circumsporozoite Protein of <i>Plasmodium </i><i>f</i><i>alciparum</i>
  作者：Christian Bisang、Luyong Jiang、Ernst Freund、Fabienne Emery、Christian Bauch、Hugues Matile、Gerd Pluschke、John A. Robinson

  DOI：10.1021/ja980444j

  日期：1998.8.1

  The immunodominant central portion of the circumsporozoite (CS) surface protein of the malaria parasite Plasmodium falciparum contains a tetrapeptide motif, Asn-Pro-Asn-Ala (NPNA), tandemly repeated almost 40 times. The three-dimensional structure of the CS protein, including the central repeat region, is presently unknown. We have investigated an approach to stabilize beta-turns in a single NPNA motif, by its incorporation into a template-bound cyclic peptide comprising the sequence ANPNAA. The template was designed to stabilize beta-turns in the peptide loop and to allow its conjugation to T-cell epitopes in a multiple antigen-peptide. NMR studies and MD simulations with time-averaged NOE-derived upper distance restraints support the formation of a stable beta-I turn conformation in the NPNA motif of this template-bound antigen. Balb/c mice immunized with a multiple-antigen-peptide containing four copies of the template-bound loop conjugated to a single universal T-cell epitope produced antibodies that bound P. falciparum sporozoites in immunofluorescence assays. These results provide further support for the immunological relevance of a type-I beta-turn conformation based on the NPNA cadence in the repeat region of the CS protein and illustrate the use of a novel template for the evaluation of conformationally constrained peptide immunogens.