sulfosuccinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: sulfosuccinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate
• 英文别名: 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt；4-(maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium；4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid sulfosuccinimide sodium salt；sodium sulfonatosuccinimido 4-(N-maleimidomethyl)cyclohexane-1-carboxylate；sodium sulfosuccinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate；sodium sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate；sodium;1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonate
• 化学式: C₁₆H₁₇N₂O₉S*Na
• 分子量: 436.375
• InChiKey: VUFNRPJNRFOTGK-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.15
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  167
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  sulfosuccinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate 在 氯化铵 作用下， 以 aq. phosphate buffer 为溶剂， 反应 1.0h， 生成 4-(N-maleimidomethyl)cyclohexane-1-carboxamide
  参考文献：
  名称：

  丁二酰亚胺为基础的结合物提高IsoDGR环肽亲到α v β 3而不促进整合变构性活化

  摘要：

  isoDGR序列是整联蛋白结合基序，已成功用作肿瘤血管结构归巢分子或用于将药物和诊断剂靶向递送至肿瘤。在这种情况下，我们以前证明了环肽2，即c（CGisoDGRG）（1）与4-（N-马来酰亚胺甲基）环己烷-1-羧酰胺缀合的产物，可以成功地用作纳米药物的肿瘤归巢配体。传递到肿瘤组织。这里，结合NMR，计算，和生物化学方法，我们表明，琥珀酰亚胺环中含有2有助于稳定的相互作用与α v β 3，在肿瘤血管中过度表达的整合素。此外，我们证明了包含嵌入在不同的分子骨架的isoDGR序列不同环肽不诱导α v β 3的变构激活和工作作为纯整联蛋白拮抗剂。这些结果可以被有益地开发用于新的基于isoDGR配体和肿瘤靶向分子的合理设计具有改进的α v β 3 -结合性质并且没有不利的整合素活化的效果。

  DOI：

  10.1021/acs.jmedchem.8b00745

文献信息

• Rapid, Stable, Chemoselective Labeling of Thiols with Julia-Kocieński-like Reagents: A Serum-Stable Alternative to Maleimide-Based Protein Conjugation
  作者：Narihiro Toda、Shigehiro Asano、Carlos F. Barbas

  DOI：10.1002/anie.201306241

  日期：2013.11.25

  Exquisite chemoselectivity for cysteine has been found for methylsulfonylphenyloxadiazole compounds under various buffer conditions. Furthermore, the resulting protein conjugates have superior stability to cysteine–maleimide conjugates in human plasma (HSA=human serum albumin, MBP‐C‐HA=maltose‐binding protein). This new thiol‐click reaction offers a new approach to generate stable protein conjugates

  已发现在各种缓冲条件下甲基磺酰基苯基恶二唑化合物对半胱氨酸具有精确的化学选择性。此外，所得到的蛋白质偶联物比人血浆中的半胱氨酸-马来酰亚胺偶联物（HSA=人血清白蛋白，MBP-C-HA=麦芽糖结合蛋白）具有更好的稳定性。这种新的硫醇点击反应为生成稳定的蛋白质偶联物和聚乙二醇化蛋白质提供了一种新方法。
• 一种联吡啶衍生物及合成方法、用途
  申请人：章健

  公开号：CN109180571B

  公开（公告）日：2021-08-13

  本发明提供了一种联吡啶化合物，该联吡啶化合物的穴状化合物产品是一类在发光和照明、荧光探针等领域显示出潜在应用前景的荧光材料，可以完全改变目前解离‑增强时间分辨荧光免疫分析法(DELFLA)缺点，实现高灵敏、大通量、全自动时间分辨免疫荧光检测。
• EDB-FN Targeted Peptide–Drug Conjugates for Use against Prostate Cancer
  作者：Shang Eun Park、Kiumars Shamloo、Timothy A. Kristedja、Shaban Darwish、Marco Bisoffi、Keykavous Parang、Rakesh Kumar Tiwari

  DOI：10.3390/ijms20133291

  日期：——

  Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can differentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buffered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 h. Confocal microscopy studies demonstrated increased binding of ligand 8 to EDB-FN compared to ligand 1. Therefore, we hypothesized that the EDB-FN targeted peptides (1 and 8) conjugated with an anticancer drug via a hydrolyzable linker would provide selective cytotoxicity to the cancer cells. To test our hypothesis, we selected both the normal prostate cell line, RWPE-1, and the cancerous prostate cell lines, PC3, DU-145, LNCaP, and C4-2, to evaluate the anticancer activity of synthesized peptide–drug conjugates. Docetaxel (Doce) and doxorubicin (Dox) were used as anticancer drugs. Dox conjugate 13 containing disulfide linkage showed comparable cytotoxicity versus Dox after 72 h incubation in all the cancer cell lines, whereas it was found to be less cytotoxic on RWPE-1, suggesting that it can act as a Dox prodrug. Doce conjugate 14 was found to be less cytotoxic in all the cell lines as compared to drug alone.

  前列腺癌（PCa）是男性最常见的恶性肿瘤，也是男性癌症相关死亡的主要原因。之前发现一种二硫键环肽配体[CTVRTSADC] 1可以针对细胞外基质中的额外区域B的纤维连接蛋白（EDB-FN），从而区分侵袭性PCa和良性前列腺增生。我们通过酰胺环化合成和优化配体1的稳定性，得到了[KTVRTSADE] 8，使用Fmoc/tBu固相化学方法。优化的靶向配体8在磷酸盐缓冲盐水（PBS，pH 6.5、7.0和7.5）和氧化还原条件下均稳定，半衰期长达8小时以上。共聚焦显微镜研究表明，与配体1相比，配体8与EDB-FN的结合增强。因此，我们假设将EDB-FN靶向肽（1和8）通过可水解连接剂与抗癌药物结合，可以提供选择性细胞毒性作用于癌细胞。为了验证我们的假设，我们选择了正常前列腺细胞系RWPE-1和癌性前列腺细胞系PC3、DU-145、LNCaP和C4-2，评估合成的肽-药物结合物的抗癌活性。Docetaxel（Doce）和doxorubicin（Dox）被用作抗癌药物。含有二硫键连接的Dox结合物13在所有癌细胞系中与Dox相比显示出可比的细胞毒性，而在RWPE-1上的细胞毒性较低，表明它可以作为Dox前药。Doce结合物14在所有细胞系中的细胞毒性均较药物单独使用时低。
• [EN] PEPTIDES FOR ACTIVATION OF CELL SIGNALING IN OSTEOPROGENITOR CELLS<br/>[FR] PEPTIDES POUR L'ACTIVATION DE LA SIGNALISATION CELLULAIRE DANS DES CELLULES OSTÉOPROGÉNITRICES
  申请人：UNIV CALIFORNIA

  公开号：WO2020018941A1

  公开（公告）日：2020-01-23

  The present invention provides compounds and pharmaceutical compositions of peptidomimetic ligands. The peptidomimetic ligands can be conjugated with phosphonate drugs. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the α4β1 integrin on mesenchymal stem cells and for the surface of bone.

  本发明提供了肽类模拟配体的化合物和制药组合物。这些肽类模拟配体可以与膦酸盐药物结合。本发明的化合物和制药组合物由于其对于骨髓干细胞上的α4β1整合素和骨表面的特异性而可用于治疗骨质疏松症和促进骨生长。
• [EN] LLP2A-BISPHOSPHONATE CONJUGATES FOR OSTEOPOROSIS TREATMENT<br/>[FR] CONJUGUÉS LLP2A-BISPHOSPHONATE POUR LE TRAITEMENT DE L'OSTÉOPOROSE
  申请人：UNIV CALIFORNIA

  公开号：WO2013032527A1

  公开（公告）日：2013-03-07

  The present invention provides compounds and pharmaceutical compositions of a peptidomimetic ligand, e.g. LLP2A, conjugated with a bisphosphonate drug, e.g. Alendronate. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the α4β1 integrin on mesenchymal stem cells and for the surface of bone.

  本发明提供了一种肽类模拟配体化合物和制药组合物，例如LLP2A，与双磷酸盐药物，例如阿伦膦酸，结合。本发明的化合物和制药组合物由于对间充质干细胞上的α4β1整合素和骨表面的特异性，对骨质疏松症的治疗和促进骨生长具有用处。