N-ε-maleimido α-(tert-butyloxycarbonyl)-L-lysine | 159684-06-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-ε-maleimido α-(tert-butyloxycarbonyl)-L-lysine
• 英文别名: Nε-maleoyl-α-(Boc)-L-lysine；N^ε-maleoyl-α-(tert-butyloxycarbonyl)-L-lysine；(S)-2-((tert-Butoxycarbonyl)amino)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoic acid；(2S)-6-(2,5-dioxopyrrol-1-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid
• CAS: 159684-06-7
• 化学式: C₁₅H₂₂N₂O₆
• 分子量: 326.349
• InChiKey: UCGBNEBUVCPALV-JTQLQIEISA-N

物化性质

• 沸点：
  533.7±45.0 °C(Predicted)
• 密度：
  1.257±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-ε-maleimido α-(tert-butyloxycarbonyl)-L-lysine 在 盐酸 、 triethylacetate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-2-hexadecanoylamino-hexanoic acid
  参考文献：
  名称：

  鲑鱼降钙素的水溶性、不可逆脂质缀合物：合成、表征和体内活性。

  摘要：

  目的：评估一种以棕榈酸为模型脂质的新型、不可逆、水基脂质化策略与鲑鱼降钙素 (sCT) 的结合。材料与方法：由棕榈酸N-琥珀酰亚胺酯与ε-马来酰亚胺赖氨酸反应合成棕榈酸水溶性ε-马来酰亚胺赖氨酸衍生物。后者由 α-Boc-赖氨酸和吡咯羧酸甲酯反应生成，随后 Boc 基团脱保护。棕榈衍生物进一步通过硫醚键与 sCT 共轭以在水溶液中产生 Mal-sCT。Mal-sCT 的身份和纯度通过电喷雾电离质谱 (ESI-MS) 和 HPLC 确认。结果：Mal-sCT 的产率为 83%。动态光散射和圆二色性数据表明，Mal-sCT 在不同极性的水溶液中呈现为稳定的螺旋结构，在浓度高于 11 microM 时具有聚集的倾向。在 Caco-2 细胞模型中，Mal-sCT 的细胞摄取是 sCT 的两倍，并且偶联物对肝酶降解的抵抗力更强。当在大鼠模型中以 0.114 mg/kg 的 sCT 等效剂量皮下给药时，Mal-sCT

  DOI：

  10.1007/s11095-006-9128-9
• 作为产物：
  描述：

  马来酸酐 、 N-alpha-叔丁氧羰基-L-赖氨酸 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-ε-maleimido α-(tert-butyloxycarbonyl)-L-lysine
  参考文献：
  名称：

  无基因组病毒衣壳作为紫杉醇递送的多价载体

  摘要：

  通过特洛伊木马递送：化学治疗剂紫杉醇的水溶性衍生物被合成，具有生物偶联功能，并附着在噬菌体 MS2 的衣壳上（见图）。当与 MCF-7 细胞孵育时，修饰的衣壳保持其形式并释放紫杉醇。由此产生的细胞活力水平与在溶液中用游离紫杉醇处理时观察到的相似。

  DOI：

  10.1002/anie.200902426

文献信息

• LINKER FOR ANTIBODY-DRUG CONJUGATES AND ITS USE
  申请人：RemeGen Co., Ltd.

  公开号：US20220072137A1

  公开（公告）日：2022-03-10

  The present invention provides a linker for preparing antibody-drug conjugates and antibody-drug conjugates prepared by the linker, as well as use of the antibody-drug conjugates in a medicament for treating tumor. The linker is capable of coupling simultaneously with the thiol group or amino group on the antibody or functional fragment of the antibody, especially it is capable of coupling with 2, 3 or 4 thiol groups on the antibody or functional fragment of the antibody. A coupled product is uniform and structurally stable.

  本发明提供了一种用于制备抗体药物偶联物的连接体，以及由该连接体制备的抗体药物偶联物，以及将抗体药物偶联物用于治疗肿瘤的药物的使用。该连接体能够同时耦合于抗体或抗体的功能片段上的巯基或氨基，特别是它能够与抗体或抗体功能片段上的2、3或4个巯基耦合。耦合产物均匀且结构稳定。
• Preparation of Asymmetric Urea Derivatives that Target Prostate-Specific Membrane Antigen for SPECT Imaging
  作者：Naoya Harada、Hiroyuki Kimura、Masahiro Ono、Hideo Saji

  DOI：10.1021/jm400895s

  日期：2013.10.24

  Prostate-specific membrane antigen (PSMA) has been identified as a diagnostic and therapeutic target for prostate cancer. (S)-2-[3-[(R)-1-Carboxy-2-mercaptoethyl]ureido-pentanedioic acid (Cys-CO-Glu) were used to design novel PSMA targeting probes by nucleophilic conjugate addition between cysteine and maleimide based reagents. 3 ([I-123]IGLCE) was synthesized by this strategy and showed high affinity for PSMA. Results of binding inhibition assays of these derivatives suggested the importance of an aromatic group and succinimide moiety for high affinity. [I-123]3 was evaluated in vivo with PSMA positive LNCaP and PSMA negative PC-3 human prostate cancer xenograft bearing mice. [I-125]3 accumulated in LNCaP tumors but not in PC-3 tumors, and the accumulation was inhibited by 2-(phosphonomethyl)pentanedioic acid (2-PMPA). Use of [I-123]3 provided positive images of LNCaP tumors in single photon emission tomography scans. These results warrant further evaluation of [I-123]3 and its derivatives as radiolabeled probes for the diagnosis of prostate cancer.
• WO2008/34124
  申请人：——

  公开号：——

  公开（公告）日：——
• A Novel Radioiodination Reagent for Protein Radiopharmaceuticals with <scp>l</scp>-Lysine as a Plasma-Stable Metabolizable Linkage To Liberate <i>m</i>-Iodohippuric Acid after Lysosomal Proteolysis
  作者：Kouji Wakisaka、Yasushi Arano、Takashi Uezono、Hiromichi Akizawa、Masahiro Ono、Keiichi Kawai、Yoshiro Ohomomo、Morio Nakayama、Hideo Saji

  DOI：10.1021/jm9606397

  日期：1997.8.1

  Radiochemical design of polypeptides using metabolizable linkages would be attractive to enhance target-selective localization of radioactivity for diagnostic and therapeutic nuclear medicine. However, while use of ester bonds as the linkage allows selective release of the designed radiometabolite from covalently conjugated polypeptides after lysosomal proteolysis in nontarget tissues, low plasma stability of ester bonds causes a decrease in radioactivity levels of the target. In pursuit of new metabolizable linkages that provide stable attachment of radiolabels with polypeptide in plasma while facilitating rapid and selective release of designed radiometabolites of rapid urinary excretion in lysosomes, a new radioiodination reagent with L-lysine as the metabolizable Linkage to liberate m-iodohippuric acid (L-HML) was designed and synthesized. Stabilities of the metabolizable linkage in serum and cleavabilities of the linkage in lysosomal proteolysis in hepatic cells were investigated after conjugation of [I-131]-L-HML with galactosyl-neoglycoalbumin (NGA). For comparison, a radioiodination reagent with an ester bond to release m-iodohippuric acid (MIH) was conjugated with NGA under similar conditions. When incubated in human serum, [I-131]-L-HML-NGA liberated less than 3% of the initial radioactivity after 24 h, whereas [I-125]MIH-NGA released more than 60% of its radioactivity during the same interval. In biodistribution studies, [I-131]-L-HML-NGA demonstrated radioactivity elimination from murine liver at a rate and excretion route similar to [I-125]MIH-NGA. Analyses of murine urine after injection of [I-131]-L-HML-NGA indicated a single radioactivity peak at fractions identical to those of m-iodohippuric acid. Biodistribution studies of radioiodinated NGAs with D-lysine or cadaverine as the linkages demonstrated a delayed elimination rate from murine liver with significantly higher radioactivity being excreted in the feces at 24 h postinjection. Thus, L-HML is the first reagent that allows stable attachment of radiolabel with polypeptide in serum while facilitating selective release of a radiometabolite with rapid urinary excretion from covalently conjugated polypeptides after lysosomal proteolysis at a rate similar to that of ester bonds. Thus, L-HML is potentially useful for the radioiodination of polypeptides for diagnostic and therapeutic purposes.
• Aqueous-Soluble, Non-Reversible Lipid Conjugate of Salmon Calcitonin: Synthesis, Characterization and In Vivo Activity
  作者：Weiqiang Cheng、Seetharama Satyanarayanajois、Lee-Yong Lim

  DOI：10.1007/s11095-006-9128-9

  日期：2007.1

  PURPOSE: A novel, non-reversible, aqueous-based lipidization strategy with palmitic acid as a model lipid was evaluated for conjugation with salmon calcitonin (sCT). MATERIALS AND METHODS: A water-soluble epsilon-maleimido lysine derivative of palmitic acid was synthesized from reaction of palmitic acid N-succinimidyl ester and epsilon-maleimido lysine. The latter was generated from reaction of alpha-Boc-lysine

  目的：评估一种以棕榈酸为模型脂质的新型、不可逆、水基脂质化策略与鲑鱼降钙素 (sCT) 的结合。材料与方法：由棕榈酸N-琥珀酰亚胺酯与ε-马来酰亚胺赖氨酸反应合成棕榈酸水溶性ε-马来酰亚胺赖氨酸衍生物。后者由 α-Boc-赖氨酸和吡咯羧酸甲酯反应生成，随后 Boc 基团脱保护。棕榈衍生物进一步通过硫醚键与 sCT 共轭以在水溶液中产生 Mal-sCT。Mal-sCT 的身份和纯度通过电喷雾电离质谱 (ESI-MS) 和 HPLC 确认。结果：Mal-sCT 的产率为 83%。动态光散射和圆二色性数据表明，Mal-sCT 在不同极性的水溶液中呈现为稳定的螺旋结构，在浓度高于 11 microM 时具有聚集的倾向。在 Caco-2 细胞模型中，Mal-sCT 的细胞摄取是 sCT 的两倍，并且偶联物对肝酶降解的抵抗力更强。当在大鼠模型中以 0.114 mg/kg 的 sCT 等效剂量皮下给药时，Mal-sCT