CCL-34

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: CCL-34
• 英文别名: TLR4 agonist CCL-34；N-[(2S)-1-oxo-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1-(undecylamino)propan-2-yl]dodecanamide
• 化学式: C₃₂H₆₂N₂O₈
• 分子量: 602.853
• InChiKey: RHZGTZCSKQCTKA-JZYYMOCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  42
• 可旋转键数：
  26
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  158
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  正十一胺 在 哌啶 、 N-甲基吗啉 、 甲醇 、 sodium methylate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.33h， 生成 CCL-34
  参考文献：
  名称：

  丝氨酸基糖脂的合成作为潜在的TLR4活化剂†

  摘要：

  通过改变α-GalCer衍生的前导化合物（CCL-34）的脂链长度和糖结构，合理设计了一系列新的不含磷酸基的单糖基糖脂，带有两个脂链），这是一种有效的TLR4激动剂。在稳定表达人TLR4，MD2和CD14（293-hTLR4 / MD2-CD14）的HEK293细胞系中测量了包含60个成员的具有不同脂质链长度的化合物的基于半乳糖基丝氨酸的合成文库的NF-κB活性。结果表明，脂胺和脂肪酸激活TLR4的最佳碳链长度分别为10-11和12。对包含具有各种糖基部分和固定脂链长度的化合物的20元合成基于糖基丝氨酸的脂质文库的评估表明，CCL-34中的半乳糖部分可以被取代葡萄糖而不会丧失活性（CCL-34-S3和CCL-34-S16）。改变CCL-34的异头糖苷键的方向导致活性完全丧失（β-CCL34）。令人惊讶地，糖基糖脂中的异头糖苷键的构型变化是可忍受的（CCL-34-S14）。另一个值得注意的发

  DOI：

  10.1039/c0ob00990c

文献信息

• A synthetic analog of α-galactosylceramide induces macrophage activation via the TLR4-signaling pathways
  作者：Ling-Chien Hung、Chun-Cheng Lin、Shih-Kai Hung、Bing-Ching Wu、Mi-Dan Jan、Sheng-Hung Liou、Shu-Ling Fu

  DOI：10.1016/j.bcp.2007.03.006

  日期：2007.6

  a-Galactosylceramide (a-GalCer), a bioactive glycolipid isolated from the marine sponge Agelas mauritianus, is a potent immunomodulator with therapeutic potential for the treatment of autoimmune diseases and cancer. The Toll-like receptor 4 (TLR4:), one of the promising molecular targets for immune-modulating drugs, is commonly expressed in innate immune cells especially macrophages and dendritic cells. Currently, whether alpha-GalCer can activate TLR4 signaling pathways remains unreported. In this study, we examined the effects of alpha-GalCer and its various structural analogs, CCL-1 similar to 47, on TLR4 activation. We found that one a-GalCer analog (CCL-34), but not a-GalCer itself, strongly stimulated NF-kappa B activity in RAW 264.7 cells. CCL-34 activated NF-kappa B in a TLR4-dependent manner and stimulated TNF-alpha production in bone marrow cells of TLR4-functional C3H/HeN mice but not in those of TLR4-defective C3H/HeJ mice. Furthermore, CCL-34 treatment stimulated NF-kappa B activation and IL-8 production in a 293 cell line constitutively expressing human TLR4, MD-2 and CD14. Treatment of RAW 264.7 cells with CCL-34 also activated TLR4-downstream mitogen-activated protein kinases (ERK, JNK and p38), induced expression of TLR4-downstream genes (TNF-alpha, IL-6, IL-1 beta and iNOS) and promoted production of cytokines characteristic of activated macrophages. CCL-34-treated RAW 264.7 cells acquired a distinct morphology similar to that of LPS-activated macrophages and exhibited higher phagocytotic activity. Moreover, treatment with a TLR4-neutalizing antibody inhibited the CCL-34-induced morphological alteration. In summary, we identify a novel synthetic compound CCL-34 that can activate macrophages via TLR4-dependent signaling pathways. Our results suggest that CCL-34 is an immune modulator and may serve as a potential drug lead for immunotherapy. (c) 2007 Elsevier Inc. All rights reserved.
• Synthesis of serine-based glycolipids as potential TLR4 activators
  作者：Li-De Huang、Hong-Jyune Lin、Po-Hsiung Huang、Wei-Chen Hsiao、L. Vijaya Raghava Reddy、Shu-Ling Fu、Chun-Cheng Lin

  DOI：10.1039/c0ob00990c

  日期：——

  orientation of the anomeric glycosidic bond of CCL-34 resulted in a complete loss of activity (β-CCL34). Surprisingly, a change in configuration of the anomeric glycosidic bond in a glucosyl glycolipid is tolerable (CCL-34-S14). Another noteworthy observation is that the activity of a L-fucosyl derived glycolipid (CCL-34-S13) was comparable to that of CCL-34. In sum, this study determines the structural

  通过改变α-GalCer衍生的前导化合物（CCL-34）的脂链长度和糖结构，合理设计了一系列新的不含磷酸基的单糖基糖脂，带有两个脂链），这是一种有效的TLR4激动剂。在稳定表达人TLR4，MD2和CD14（293-hTLR4 / MD2-CD14）的HEK293细胞系中测量了包含60个成员的具有不同脂质链长度的化合物的基于半乳糖基丝氨酸的合成文库的NF-κB活性。结果表明，脂胺和脂肪酸激活TLR4的最佳碳链长度分别为10-11和12。对包含具有各种糖基部分和固定脂链长度的化合物的20元合成基于糖基丝氨酸的脂质文库的评估表明，CCL-34中的半乳糖部分可以被取代葡萄糖而不会丧失活性（CCL-34-S3和CCL-34-S16）。改变CCL-34的异头糖苷键的方向导致活性完全丧失（β-CCL34）。令人惊讶地，糖基糖脂中的异头糖苷键的构型变化是可忍受的（CCL-34-S14）。另一个值得注意的发