N-(9H-fluoren-9-yl)methoxycarbonyl-O-(2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl]α-D-galactopyranosyl)-L-serine | 125760-30-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(9H-fluoren-9-yl)methoxycarbonyl-O-(2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl]α-D-galactopyranosyl)-L-serine
• 英文别名: Fmoc-Ser(Ac4Gal-(β1->3)-α-Ac2GalNAc)-OH；Fmoc-(Ac₄Galβ1,3Ac₂GalNAcα1→)Ser；Fmoc-Ser(Ac4Galβ1-3Ac2GalNAcα-O-)-OH；N-(9H-fluoren-9-ylmethoxycarbonyl)-O-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-(1,3)-2-acetamido-4,6-di-O-acetoxy-2-deoxy-α-D-galactopyranosyl]-L-serine；Fmoc-Ser(Ac₄Galβ1-3Ac₂GalNAcα)-OH；Fmoc-L-Ser(TF)-OH；(2S)-3-[(2S,3R,4R,5R,6R)-3-acetamido-5-acetyloxy-6-(acetyloxymethyl)-4-[(2R,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 125760-30-7
• 化学式: C₄₄H₅₂N₂O₂₁
• 分子量: 944.898
• InChiKey: JIIREWDIFSHWID-CYAMVCNPSA-N

物化性质

• 沸点：
  995.1±65.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  67
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  299
• 氢给体数：
  3
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  N-(9H-fluoren-9-yl)methoxycarbonyl-O-(2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl]α-D-galactopyranosyl)-L-serine 在 吗啉 、 sodium methylate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (β-D-galactopyranosyl-(1->3)-2-acetamido-2-deoxy-α-D-galactopyranosyl)-N-acetyl-3-O-L-seryl)biotinaminocaproyl hydrazide
  参考文献：
  名称：

  生物素化的T-抗原-丝氨酸衍生物的合成中发生异常的内酰胺形成

  摘要：

  描述了通过α（7α）或β（7β）2-乙酰氨基-2-脱氧-D-半乳糖苷键与丝氨酸连接的生物素化的T-抗原的合成。这些衍生物对于检测黑色素瘤细胞表面和/或迁移途径上的特定内源性凝集素是必需的。在合成过程中，与叠氮二糖5β的β端基异构体一起观察到异常的内酰胺形成。

  DOI：

  10.1016/s0008-6215(97)00146-8
• 作为产物：
  描述：

  N-(9H-fluoren-9-yl)methoxycarbonyl-O-(2-acetamido-2-deoxy-4,6-O-p-methoxybenzylidene-α-D-galactopyranosyl)-L-serine tert-butyl ester 在 ammonium cerium(IV) nitrate 、 4 A molecular sieve 、 氰化汞 、 三氟乙酸 作用下， 以 吡啶 、 硝基甲烷 、 二氯甲烷 、 苯甲醚 、 乙腈 为溶剂， 反应 34.75h， 生成 N-(9H-fluoren-9-yl)methoxycarbonyl-O-(2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl]α-D-galactopyranosyl)-L-serine
  参考文献：
  名称：

  上皮钙粘蛋白同源识别域的肽和糖肽部分结构的合成

  摘要：

  采用Fmoc策略，基于酸敏感Wang锚固相技术合成上皮钙粘蛋白(E-cadherin)的同源识别位点的肽和糖肽序列。制备了具有 TN-、T-、(2-6)-唾液酸 T-抗原和 β-N-乙酰氨基葡萄糖侧链的 Fmoc 丝氨酸结构单元，用于构建 E-钙粘蛋白糖肽。T-和(2-6)-唾液酸T-丝氨酸衍生物已通过带有Fmoc/叔丁酯保护基组合的TN-抗原丝氨酸衍生物的化学糖基化获得。根据 NOESY 和 ROESY NMR 实验，在 N 端未酰化的 E-钙粘蛋白（糖）肽在水中更喜欢转弯型构象。

  DOI：

  10.1055/s-2003-42429

文献信息

• Synthesis of Tn/T Antigen MUC1 Glycopeptide BSA Conjugates and Their Evaluation as Vaccines
  作者：Hui Cai、Zhi-Hua Huang、Lei Shi、Peng Zou、Yu-Fen Zhao、Horst Kunz、Yan-Mei Li

  DOI：10.1002/ejoc.201100304

  日期：2011.7

  The tumor-associated mucin MUC1 over-expressed in most epithelial tumor tissues is considered a promising target for immunotherapy. The extracellular part of MUC1 contains a domain of numerous tandem repeats of the amino acid sequence HGVTSAPDTRPAPGSTAPPA, including five potential O-glycosylation sites. In this study, T9 and S15 have been chosen as the positions of glycosylation. The glycopeptides N-terminally

  在大多数上皮肿瘤组织中过度表达的肿瘤相关粘蛋白 MUC1 被认为是免疫治疗的有希望的靶点。MUC1 的细胞外部分包含氨基酸序列 HGVTSAPDTRAPPGSTAPPA 的众多串联重复结构域，包括五个潜在的 O-糖基化位点。在本研究中，选择了 T9 和 S15 作为糖基化的位置。通过微波辅助 Fmoc 固相肽合成法合成了 N 端带有三甘醇间隔物的糖肽。从树脂上分离并脱保护后，将 MUC1 糖肽与牛血清白蛋白 (BSA) 结合。为了评估免疫学特性，用这些 BSA 疫苗免疫 balb/c 小鼠。
• Effects of the multiple O-glycosylation states on antibody recognition of the immunodominant motif in MUC1 extracellular tandem repeats
  作者：Shobith Rangappa、Gerard Artigas、Risho Miyoshi、Yasuhiro Yokoi、Shun Hayakawa、Fayna Garcia-Martin、Hiroshi Hinou、Shin-Ichiro Nishimura

  DOI：10.1039/c6md00100a

  日期：——

  regions, on antibody recognition. In this study, we established a comprehensive approach for the characterization of anti-MUC1 antibodies by combining microarray-based epitope profiling and NMR-based conformational analysis of synthetic MUC1 glycopeptides. Epitope mapping analysis using a microarray that displayed 23 synthetic MUC1 glycopeptides revealed that anti-KL6/MUC1 monoclonal antibody (anti-KL6

  与人上皮细胞膜MUC1糖蛋白以异常糖型反应的抗体在各种癌症和间质性肺病中是很有前途的诊断和治疗试剂。但是，抗MUC1抗体的确切表位仍不清楚。尽管MUC1胞外域在串联重复序列中有多个O-糖基化位点，但几乎没有系统的方法来确定多个O-的影响在与疾病相关的表位区域的背景下，在抗体识别中的β-糖基化状态。在这项研究中，我们通过结合基于微阵列的表位分析和合成MUC1糖肽的基于NMR的构象分析，建立了表征MUC1抗体的综合方法。使用显示23种合成MUC1糖肽的微阵列进行的表位作图分析显示，抗KL6 / MUC1单克隆抗体（抗KL6 mAb）与必需表位Pro-Asp-Thr [Neu5Acα（2→3）Galβ（ 1→3）GalNAcα1→] -Arg-Pro-Ala-Pro，与针对相同Pro-Asp-Thr的其他经过深入研究的抗MUC1单抗DF3和SM3相比，最终具有糖型特异性串联重复的-Arg（PDT
• Structure−Activity Relationship Studies for the Peptide Portion of the Bladder Epithelial Cell Antiproliferative Factor from Interstitial Cystitis Patients
  作者：Piotr Kaczmarek、Susan K. Keay、Gillian M. Tocci、Kristopher R. Koch、Chen-Ou Zhang、Joseph J. Barchi、David Grkovic、Li Guo、Christopher J. Michejda

  DOI：10.1021/jm8002763

  日期：2008.10.9

  We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelia] and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase methods using standard Fmoc chemistry and purified by RP-HPLC; all intermediate and final products were verified by HPLC-MS and NMR analyses. Antiproliferative activity of each derivative was determined by inhibition of (3)H-thymidine incorporation in primary normal human bladder epithelial cells. Structural components of the peptide segment of APF that proved to be important for biological activity included the presence of at least eight of the nine N-terminal amino acids, a negative charge in the C-terminal amino acid, a free amino group at the N-terminus, maintenance of a specific amino acid sequence in the C-terminal tail, and trans conformation for the peptide bonds. These data provide critical guidelines for optimization of structure in design of APF analogues as potential therapeutic agents.
• Saccharide-Induced Peptide Conformation in Glycopeptides of the Recognition Region of LI-Cadherin
  作者：Axel Kuhn、Horst Kunz

  DOI：10.1002/anie.200602494

  日期：2007.1.8
• Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis
  作者：Yalong Zhang、Saddam M. Muthana、David Farnsworth、Olaf Ludek、Kristie Adams、Joseph J. Barchi、Jeffrey C. Gildersleeve

  DOI：10.1021/ja212188r

  日期：2012.4.11

  Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.