N-(fluoren-9-ylmethoxycarbonyl)-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threonine benzyl ester | 100938-56-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(fluoren-9-ylmethoxycarbonyl)-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threonine benzyl ester
• 英文别名: N^α-fluoren-9-ylmethoxycarbonyl-O-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threoninebenzyl ester；N-(9H-fluorene-9-yl)-methoxycarbonyl-O-(3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-threonine benzyl ester；benzyl (2S,3R)-3-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoate
• CAS: 100938-56-5
• 化学式: C₄₀H₄₄N₂O₁₃
• 分子量: 760.795
• InChiKey: ABZMXOHASDDUCE-VINLKNQHSA-N

物化性质

• 沸点：
  901.2±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  55.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  191.09
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  N-(fluoren-9-ylmethoxycarbonyl)-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threonine benzyl ester 在 吗啉 作用下， 反应 0.5h， 以86%的产率得到(2S,3R)-2-Amino-3-((2S,3R,4R,5R,6R)-4,5-diacetoxy-6-acetoxymethyl-3-acetylamino-tetrahydro-pyran-2-yloxy)-butyric acid benzyl ester
  参考文献：
  名称：

  具有TN和T抗原结构的糖肽的合成及其与牛血清白蛋白的偶联。

  摘要：

  合成了具有TN和T抗原结构的糖肽，这些肽代表具有血型M特异性的去唾液酸糖蛋白的N端三肽，已使用芴基甲氧基羰基（Fmoc）和2-吡啶基乙氧基羰基（Pyoc）基团进行氨基保护，并使用苄基酯作为羧基封闭基团来合成糖肽功能。Fmoc和Pyoc基团可以通过在碱敏感的O-糖基丝氨酸和-苏氨酸键稳定的条件下用弱碱吗啉处理而除去。用甲醇肼从碳水化合物部分除去酯基，得到TN和T抗原糖肽，其通过碳二亚胺方法与牛血清白蛋白（BSA）偶联，并且没有任何间隔基。所得的缀合物每个蛋白质分子平均包含大于20个糖肽。

  DOI：

  10.1016/0008-6215(90)84081-5
• 作为产物：
  描述：

  phenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-thiol-D-galactopyranoside 在 Rh on carbon 吡啶 、 2,6-二叔丁基-4-甲基吡啶 、 三氟甲磺酸酐 、 氢气 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 氢氟酸 、 乙酸乙酯 、 甲苯 为溶剂， 生成 N-(fluoren-9-ylmethoxycarbonyl)-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-L-threonine benzyl ester
  参考文献：
  名称：

  The effects of glycosylation on peptide backbone conformation

  摘要：

  DOI：

  10.1021/ja00061a053

文献信息

• Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen-based anti-cancer vaccine candidates
  作者：Mingjing Li、Fan Yu、Chao Yao、Peng George Wang、Yonghui Liu、Wei Zhao

  DOI：10.1039/c7ob02976d

  日期：——

  Therapeutic vaccines have been regarded as a very promising treatment modality against cancer. Tumor-associated MUC1 is a promising antigen for the design of antitumor vaccines. However, body's immune tolerance and low immunogenicity of MUC1 glycopeptides limited their use as effective antigen epitopes of therapeutic vaccines. To solve this problem, we chose the immune dominant region of MUC1 VNTRs

  治疗性疫苗被认为是一种非常有前途的抗癌治疗方法。肿瘤相关性MUC1是用于设计抗肿瘤疫苗的有前途的抗原。但是，人体的免疫耐受性和MUC1糖肽的低免疫原性限制了它们作为治疗性疫苗的有效抗原表位的用途。为了解决这个问题，我们选择了MUC1 VNTRs的免疫优势区域。我们设计并合成了其线性三价糖肽片段，并将其与BSA偶联。免疫学评估表明，基于糖基化MUC1的疫苗11诱导的抗体比未糖基化10的抗体具有更强的结合力。新型构建的抗原表位具有克服天然MUC1糖肽弱免疫原性的潜力，值得进一步研究。
• Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of antibacterial activity
  作者：Sariya Talat、Menithalakshmi Thiruvikraman、Saroj Kumari、Kanwal J. Kaur

  DOI：10.1007/s10719-011-9353-2

  日期：2011.12

  antibacterial peptides, formaecin I and drosocin, were synthesized by varying the nature of sugar and its linkage with bioactive peptides to understand the influence of structure variation of glycosylation on their antibacterial activities. Higher antibacterial activities of all glycopeptides compared to their respective non-glycosylated counterparts emphasize in part the importance of sugar moieties

  合成糖肽是研究O的影响的有趣模型系统-糖基化调节它们的功能和结构。通过改变糖的性质及其与生物活性肽的连接，合成了两种抗菌肽 Formaecin I 和 drosocin 的一系列糖基化类似物，以了解糖基化结构变化对其抗菌活性的影响。与它们各自的非糖基化对应物相比，所有糖肽的更高抗菌活性部分强调了糖部分在这些肽的功能影响中的重要性。类似物之间独特差异的后果在它们的抗菌活性上是显而易见的，但通过圆二色性研究在结构上并不明显。我们已经表明，当针对几种革兰氏阴性细菌菌株进行测试时，不同糖基化的肽在彼此之间表现出不同的作用。与天然糖肽相比，Formaecin I 和drosocin 中单糖部分和/或其异头构型的变化导致抗菌活性降低，但糖基化drosocin 类似物的抗菌活性降低程度较小。可能是由于同一肽中不同糖之间的拓扑差异引起的肽构象变化导致结合特性的可能调节，这似乎是它们抗菌活性差异的原因。事实
• A Synthetic MUC1 Glycopeptide Bearing βGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells
  作者：Vanessa Leiria Campo、Thalita B. Riul、Leandro Oliveira Bortot、Maristela B. Martins-Teixeira、Marcelo Fiori Marchiori、Emanuela Iaccarino、Menotti Ruvo、Marcelo Dias-Baruffi、Ivone Carvalho

  DOI：10.1002/cbic.201600473

  日期：2017.3.16

  Anticancer immunogenicity: Glycopeptides incorporating αGalNAc‐Thr (Tn) and βGalNAc‐Thr residues as Tn antigen isomers were synthesized as mimetics of MUC1 tumor mucin glycoproteins. The unnatural βGalNAc‐glycopeptide‐BSA showed improved immunogenicity, with potential for the development of anticancer vaccines.

  抗癌免疫原性：糖肽结合了αGalNAc-Thr（Tn）和βGalNAc-Thr残基作为Tn抗原异构体，被合成为MUC1肿瘤粘蛋白糖蛋白的模拟物。非天然的βGalNAc-糖肽-BSA具有改善的免疫原性，具有开发抗癌疫苗的潜力。
• Synthetic and Immunological Studies on Clustered Modes of Mucin-Related Tn and TF O-Linked Antigens:  The Preparation of a Glycopeptide-Based Vaccine for Clinical Trials against Prostate Cancer
  作者：Scott D. Kuduk、Jacob B. Schwarz、Xiao-Tao Chen、Peter W. Glunz、Dalibor Sames、Govindaswami Ragupathi、Philip O. Livingston、Samuel J. Danishefsky

  DOI：10.1021/ja9825128

  日期：1998.12.1

  The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) and immunoconjugated to a carrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunological study. Three Tn conjugates were used to vaccinate groups of mice, and all preparations proved to be immunogenic. The Tn(c) covalently linked to KLH (27-KLH) plus the adjuvant QS-21 was the optimal vaccine, inducing high median IgM and IgG titers against Tn(c) by ELISA. These antibodies were strongly reactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancer cell Line LS-B by FAGS. The antibodies' reactivities with natural antigens were inhibited with synthetic Tn(c) but not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLH and 30-pam plus QS-21 are being tested in patients with prostate cancer.
• α-Selective glycosylation affords mucin-related GalNAc amino acids and diketopiperazines active on Trypanosoma cruzi
  作者：Maristela B. Martins-Teixeira、Vanessa L. Campo、Monica Biondo、Renata Sesti-Costa、Zumira A. Carneiro、João S. Silva、Ivone Carvalho

  DOI：10.1016/j.bmc.2013.01.027

  日期：2013.4

  This work addresses the synthesis and biological evaluation of glycosyl diketopiperazines (DKPs) cyclo[Asp-(alpha GalNAc)Ser] 3 and cyclo[Asp-(alpha GalNAc)Thr] 4 for the development of novel anti-trypanosomal agents and Trypanosoma cruzi trans-sialidase (TcTS) inhibitors. The target compounds were synthetized by coupling reactions between glycosyl amino acids alpha GalNAc-Ser 7 or alpha GalNAc-Thr 8 and the amino acid (O-tBu)-Asp 17, followed by one-pot deprotection-cyclisation reaction in the presence of 20% piperidine in DMF. The protected glycosyl amino acid intermediates 7 and 8 were, in turn, obtained by a-selective, HgBr2-catalysed glycosylation reactions of Fmoc-Ser/Thr benzyl esters 12/14 with alpha GalN(3)Cl 11, being, subsequently, fully deprotected for comparative biological assays. The DKPs 3 and 4 showed relevant anti-trypanosomal effects (IC50 282-124 mu M), whereas glycosyl amino acids 1 and 2 showed better TcTS inhibition (57-79%) than the corresponding DKPs (13-25%). (C) 2013 Elsevier Ltd. All rights reserved.