callyaerin A | 1243246-46-9

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: callyaerin A
• 英文别名: (2S)-N-[(2S,3S)-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]-1-[(3S,9S,12S,15S,18S,20R,24S,26Z,30S,33S)-12,24-bis[(2S)-butan-2-yl]-20-hydroxy-9,30-bis(2-methylpropyl)-2,8,11,14,17,23,29,32-octaoxo-15-propan-2-yl-1,7,10,13,16,22,25,28,31-nonazatetracyclo[31.3.0.03,7.018,22]hexatriacont-26-ene-27-carbonyl]pyrrolidine-2-carboxamide
• CAS: 1243246-46-9
• 化学式: C₆₉H₁₀₈N₁₄O₁₄
• 分子量: 1357.7
• InChiKey: VYGNFUUPOSIKCC-BIXVJJLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  97
• 可旋转键数：
  21
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  389
• 氢给体数：
  11
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  callyaerin A 在 盐酸 、 水 作用下， 反应 24.0h， 生成 L-苯丙氨酸
  参考文献：
  名称：

  Callyaerins A–F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa

  摘要：

  Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D (H-1, C-13 and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the template for ring closure and afforded the linkage to the peptidic side chain which was always initiated with a proline moiety. All peptides contained three or more proline residues and the remaining residues were predominantly hydrophobic residues with all amino acids present in the L form. Callyaerins A-F (1-6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 mu M, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.012
• 作为产物：
  描述：

  Ile-Hyp-Val-Ile-Leu-Pro-Pro-Leu-FGly-Pro-Ile-Phe-Gly-CONH₂ 在 甲酸 、 magnesium sulfate 作用下， 以 乙腈 为溶剂， 反应 10.0h， 以81%的产率得到callyaerin A
  参考文献：
  名称：

  Callyaerin A的全合成和构象研究：带有罕见刚性化（Z）-2,3-二氨基丙烯酰胺基团的抗管状环状肽。

  摘要：

  据报道，含有罕见的（Z）-2,3-二氨基丙烯酰胺桥连基序的抗TB环状肽callyaerin A（1）的首次合成。Fmoc-甲酰基甘氨酸-二乙缩醛在线性前驱体1的合成中用作甲酰基甘氨酸的掩蔽当量。在线性肽前体中甲酰甘氨酸残基和N-末端胺之间的分子内环化提供了大环天然产物1。它具有强大的抗结核病活性（MIC100 = 32μm），而其全酰胺同源物却没有活性。天然产物及其全酰胺类似物的可变温度NMR研究表明，该二氨基丙烯酰胺单元对肽构象具有非凡的刚性。本文报道的工作指出了（Z）-2,3-二氨基丙烯酰胺部分赋予肽生物活性的内在作用。

  DOI：

  10.1002/anie.201712792

文献信息

• Callyaerins A–F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa
  作者：Sabrin R.M. Ibrahim、Cho Cho Min、Franka Teuscher、Rainer Ebel、Christel Kakoschke、Wenhan Lin、Victor Wray、RuAngelie Edrada-Ebel、Peter Proksch

  DOI：10.1016/j.bmc.2010.06.012

  日期：2010.7

  Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D (H-1, C-13 and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the template for ring closure and afforded the linkage to the peptidic side chain which was always initiated with a proline moiety. All peptides contained three or more proline residues and the remaining residues were predominantly hydrophobic residues with all amino acids present in the L form. Callyaerins A-F (1-6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 mu M, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans. (C) 2010 Elsevier Ltd. All rights reserved.
• Total Synthesis and Conformational Study of Callyaerin A: Anti-Tubercular Cyclic Peptide Bearing a Rare Rigidifying (<i>Z</i> )-2,3- Diaminoacrylamide Moiety
  作者：Shengping Zhang、Luis M. De Leon Rodriguez、Ivanhoe K. H. Leung、Gregory M. Cook、Paul W. R. Harris、Margaret A. Brimble

  DOI：10.1002/anie.201712792

  日期：2018.3.26

  the macrocyclic natural product 1. Synthetic 1 possessed potent anti-TB activity (MIC100 =32 μm) while its all-amide congener was inactive. Variable-temperature NMR studies of both the natural product and its all-amide analogue revealed the extraordinary rigidity imposed by this diaminoacrylamide unit on peptide conformation. The work reported herein pinpoints the intrinsic role that the (Z)-2,3-diaminoacrylamide

  据报道，含有罕见的（Z）-2,3-二氨基丙烯酰胺桥连基序的抗TB环状肽callyaerin A（1）的首次合成。Fmoc-甲酰基甘氨酸-二乙缩醛在线性前驱体1的合成中用作甲酰基甘氨酸的掩蔽当量。在线性肽前体中甲酰甘氨酸残基和N-末端胺之间的分子内环化提供了大环天然产物1。它具有强大的抗结核病活性（MIC100 = 32μm），而其全酰胺同源物却没有活性。天然产物及其全酰胺类似物的可变温度NMR研究表明，该二氨基丙烯酰胺单元对肽构象具有非凡的刚性。本文报道的工作指出了（Z）-2,3-二氨基丙烯酰胺部分赋予肽生物活性的内在作用。