1S)-1-[[[(2R)-2-羧基-2-[[芴甲氧羰基]氨基]乙基]硫基]甲基]-1,2-乙二基双(十六烷酸)酯 | 139573-78-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 1S)-1-[[[(2R)-2-羧基-2-[[芴甲氧羰基]氨基]乙基]硫基]甲基]-1,2-乙二基双(十六烷酸)酯
• 中文别名: 芴甲氧羰基-S-二棕榈酰-L-半胱氨酸(S)
• 英文名称: N-fluorenylmethoxycarbonyl-S-[2,3-bis(palmitoyloxy)-(2S)-propyl]-(R)-cysteine
• 英文别名: Fmoc-Cys((S)-2,3-di(palmitoyloxy)-propyl)-OH；(2R)-3-[(2S)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 139573-78-7
• 化学式: C₅₃H₈₃NO₈S
• 分子量: 894.31
• InChiKey: HNJKCVLFJLXANK-UCNLINEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  17.8
• 重原子数：
  63
• 可旋转键数：
  42
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H302,H315,H319
• 储存条件：
  室温下密封保存，并确保干燥。

反应信息

• 作为反应物：
  描述：

  H-Gly-Gly-Gly-Glu(O-t-Bu)-Thr(t-Bu)-Thr(t-Bu)-O-t-Bu 、 1S)-1-[[[(2R)-2-羧基-2-[[芴甲氧羰基]氨基]乙基]硫基]甲基]-1,2-乙二基双(十六烷酸)酯 在 达卡巴嗪 、 HONB 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 [(2S)-3-[(2R)-3-[[2-[[2-[[2-[[(2S)-1-[[(2S,3R)-1-[[(2S,3R)-1,3-bis[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]amino]-5-[(2-methylpropan-2-yl)oxy]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-oxopropyl]sulfanyl-2-hexadecanoyloxypropyl] hexadecanoate
  参考文献：
  名称：

  Synthesis and Biological Activities of TAN-1511 Analogues.

  摘要：

  合成了TAN-1511的类药物，并检查了它们对骨髓细胞增殖的影响。要发挥有效活性，需满足以下条件：2-氨基-6, 7-二羟基-4-硫代heptanoic acid部分的构象必须为(2R, 6R)，长链酰基（C14到C18）必须与两个羟基结合，氨基必须是游离的或与长链脂肪酸（约C14）酰化，肽部分必须包含谷氨酸。在合成的化合物中，三钠(2R, 6R)-2-氨基-6, 7-双（十六酰氧基）-4-硫代heptanoyl甘氨酸谷氨酰谷氨酸，由于其溶解度提高，在小鼠的实验性白细胞减少症中表现出有效性。

  DOI：

  10.7164/antibiotics.48.589
• 作为产物：
  描述：

  (R)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-mercaptopropanoate 在 4-二甲氨基吡啶 、 达卡巴嗪 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 1S)-1-[[[(2R)-2-羧基-2-[[芴甲氧羰基]氨基]乙基]硫基]甲基]-1,2-乙二基双(十六烷酸)酯
  参考文献：
  名称：

  Synthesis and Biological Activities of TAN-1511 Analogues.

  摘要：

  合成了TAN-1511的类药物，并检查了它们对骨髓细胞增殖的影响。要发挥有效活性，需满足以下条件：2-氨基-6, 7-二羟基-4-硫代heptanoic acid部分的构象必须为(2R, 6R)，长链酰基（C14到C18）必须与两个羟基结合，氨基必须是游离的或与长链脂肪酸（约C14）酰化，肽部分必须包含谷氨酸。在合成的化合物中，三钠(2R, 6R)-2-氨基-6, 7-双（十六酰氧基）-4-硫代heptanoyl甘氨酸谷氨酰谷氨酸，由于其溶解度提高，在小鼠的实验性白细胞减少症中表现出有效性。

  DOI：

  10.7164/antibiotics.48.589

文献信息

• Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines
  作者：Benjamin L. Lu、Geoffrey M. Williams、Daniel J. Verdon、P. Rod Dunbar、Margaret A. Brimble

  DOI：10.1021/acs.jmedchem.9b01044

  日期：2020.3.12

  immunotherapy has gained increasing attention due to its potential specificity and lack of adverse side effects when compared to more traditional modes of treatment. Toll-like receptor 2 (TLR2) agonists are lipopeptides possessing the S-[2,3-bis(palmitoyloxy)propyl]-l-cysteine (Pam2Cys) motif and exhibit potent immunostimulatory effects. These agonists offer a means of providing “danger signals” in order

  与更传统的治疗方式相比，癌症免疫疗法由于其潜在的特异性和缺乏不良副作用而受到越来越多的关注。Toll样受体2（TLR2）激动剂是脂肽，具有S- [2,3-双（棕榈酰氧基）丙基] -1-半胱氨酸（Pam 2 Cys）基序，并表现出强大的免疫刺激作用。这些激动剂提供了一种提供“危险信号”的方式，以激活针对肿瘤抗原的免疫系统。因此，在寻找潜在的癌症免疫刺激剂方面，TLR2激动剂的开发具有吸引力。Pam 2的现有SAR研究带有TLR2的半胱氨酸表明，对活性的结构要求在大多数情况下是非常难以忍受的。我们已经研究了立体化学的重要性，N末端酰化的影响以及Pam 2 Cys结合的脂肽中两个酯官能团之间对TLR2活性的同源性。的[R非对映体是显著比更有效小号非对映体和Ñ末端修饰通常降低TLR2活性。最显着地，同源性产生了对含有天然Pam 2 Cys的构建体具有相对活性的类似物。
• Synthesis and evaluation of fluorescent Pam3Cys peptide conjugates
  作者：Geoffroy P.P. Gential、Nataschja I. Ho、Fabrizio Chiodo、Nico Meeuwenoord、Ferry Ossendorp、Herman S. Overkleeft、Gijs A. van der Marel、Dmitri V. Filippov

  DOI：10.1016/j.bmcl.2016.05.094

  日期：2016.8

  Chirally pure R- and S-epimers of TLR2 ligand Pam3CysSK4 were prepared and separately conjugated to an OVA model epitope, in which lysine was replaced by azidonorleucine. The azide function in the conjugate permitted labelling with different fluorophores by use of strain-promoted 3+2 cycloaddition. The R-epimer of the labelled conjugates induced TLR2-dependent DC maturation, while S-epimer proved to

  制备了TLR2配体Pam 3 CysSK 4的手性纯R-和S-受体，并将其分别偶联至OVA模型表位，其中赖氨酸被叠氮亮氨酸取代。通过使用应变促进的3 + 2环加成，共轭物中的叠氮化物功能允许用不同的荧光团标记。标记的结合物的R-受体诱导TLR2依赖的DC成熟，而S-受体被证明是无活性的。结合Pam 3 CysSK 4的亲脂性具有荧光团的配体以不可预测的方式影响所得缀合物的溶解度，并且仅用Cy-5标记的缀合物适用于共聚焦荧光显微镜实验。结果表明，Cy-5标记的脂肽的两个差向异构体均被很好地内化，表明不依赖TLR2的细胞摄取。提出的结果证明了应变促进的叠氮化物-炔烃环加成在高度亲脂性脂肽的标记中的有用性，而不会干扰这些缀合物在激活TLR-2方面的体外活性。
• Design, Synthesis, and Preliminary Immunological Studies of MUC1-Based Antitumor Vaccines Adjuvanted with <i>R</i>- and <i>S</i>-FSL-1
  作者：Yonghui Liu、Bocheng Yan、Zhaoyu Wang、Haomiao Zhu、Xiaona Yin、Kun Wang、Menglei Wang、Wei Zhao

  DOI：10.1021/acsmedchemlett.9b00579

  日期：2020.7.9

  Fibroblast stimulating lipopeptide 1 (FSL-1) is the ligand of TLR2 and TLR6 and can be used as the vaccine adjuvant to prepare antitumor vaccines. However, FSL-1 is a stereoisomeric mixture that contains the R stereoisomer and S stereoisomer, and it is still unclear which stereoisomer has better adjuvant activities. In this work, we designed and synthesized MUC1-based antitumor vaccines adjuvanted with the stereoisomers R-FSL-1 and S-FSL-1, which were synthesized from the stereoisomeric building blocks R-Fmoc-Pam(2)Cys-OH and S-Fmoc-Pam(2)Cys-OH, respectively. Immunological evaluation indicated that both R-FSL-1 and S-FSL-1 can be used as adjuvants for the construction of MUC1-based antitumor vaccines, with R-FSL-1 showing a better adjuvant effect than S-FSL-1.
• Stereochemical Dependence of the Self-Assembly of the Immunoadjuvants Pam₃Cys and Pam₃Cys-Ser
  作者：Frank Reichel、Annie M. Roelofsen、Hubertus P. M. Geurts、Taina I. Hämäläinen、Martinus C. Feiters、Geert-Jan Boons

  DOI：10.1021/ja991319q

  日期：1999.9.1

  The lipopeptide tripalmitoyl-S-glycerylcysteine (Pam(3)Cys) is derived from the N-terminal part of bacterial lipopeptides and is a polyclonal B-lymphocyte and macrophage activator. Derivatives of Pam(3)Cys constitute highly potent, nontoxic immunoadjuvants, and lipopeptide-antigen conjugates have found important applications as novel fully synthetic low-molecular-weight vaccines. To establish a possible correlation between molecular structure, aggregation properties, and biological activities, we have studied the self-assembly and monolayer properties of a range of Pam(3)Cys derivatives using transmission electron microscopy (TEM) and a Langmuir-film balance combined with a Brewster angle microscopy (BAM). It was found that the chirality of the glyceryl moiety and the additional serine unit impacted on the mode of aggregation and the monolayer properties. Correlations are discussed between these physicochemical properties and biological activities.
• Synthesis and Biological Activities of TAN-1511 Analogues.
  作者：TSUNEAKI HIDA、KOZO HAYASHI、KOICHI YUKISHIGE、SEIICHI TANIDA、NORIAKI KAWAMURA、SETSUO HARADA

  DOI：10.7164/antibiotics.48.589

  日期：——

  TAN-1511 analogues were synthesized and their effects on the proliferation of bone marrow cells were examined. To exert potent activity the following conditions are necessary: the configuration of the 2-amino-6, 7-dihydroxy-4-thiaheptanoic acid moiety must be (2R, 6R), long chain acyl groups (C14 to C18) must be bound to both hydroxyl groups, the amino group must be free or acylated with the long chain fatty acid (ca. C14) and the pep tide moiety must have glutamic acid as a component. Among the synthesized compounds, trisodium (2R, 6R)-2-amino-6, 7-bis (hexadecanoyloxy)-4-thiaheptanoyl glycyl glutamyl glutamate, which has improved solubility, was effective in experimental leukocytopenia in mice.

  合成了TAN-1511的类药物，并检查了它们对骨髓细胞增殖的影响。要发挥有效活性，需满足以下条件：2-氨基-6, 7-二羟基-4-硫代heptanoic acid部分的构象必须为(2R, 6R)，长链酰基（C14到C18）必须与两个羟基结合，氨基必须是游离的或与长链脂肪酸（约C14）酰化，肽部分必须包含谷氨酸。在合成的化合物中，三钠(2R, 6R)-2-氨基-6, 7-双（十六酰氧基）-4-硫代heptanoyl甘氨酸谷氨酰谷氨酸，由于其溶解度提高，在小鼠的实验性白细胞减少症中表现出有效性。