N-(4-氨基丁基)生物酰胺 | 151294-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 中文名称: N-(4-氨基丁基)生物酰胺
• 英文名称: 5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoic acid (4-amino-butyl)-amide
• 英文别名: 4-aminobutanamide biotin；biotin diamine；N-(4-Aminobutyl)biotinamide；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-(4-aminobutyl)pentanamide
• CAS: 151294-96-1
• 化学式: C₁₄H₂₆N₄O₂S
• 分子量: 314.452
• InChiKey: RHLVNHVKSXNHES-GVXVVHGQSA-N

物化性质

• 沸点：
  650.1±50.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

制备方法与用途

生物活性方面，Biotin-C4-amide-C5-NH2 是一种可降解 (cleavable) 的 ADC 链接剂，可用于合成抗体偶联药物 (ADC)。

| 可降解 |

体外研究显示，ADCs 由通过 ADC 链接剂连接的抗体和细胞毒性分子组成。

反应信息

• 作为反应物：
  描述：

  (S)-3-(3,4-dibenzyloxyphenoxy)-1,2-epoxypropane 、 N-(4-氨基丁基)生物酰胺 以 甲醇 为溶剂， 反应 6.0h， 以60%的产率得到XIE2008-biotin
  参考文献：
  名称：

  p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis

  摘要：

  宏自噬介导了蛋白质和非蛋白质细胞成分的选择性降解。在这里，我们展示了N-末端规则途径调节宏自噬。在这种机制中，自噬适配器p62/SQSTM1/Sequestosome-1是一个N-识别蛋白，能结合类型1和类型2的N末端降解子（N-降解子），包括精氨酸（Nt-Arg）。这两种类型的N-降解子结合其ZZ结构域。通过三维建模，我们开发了合成配体与p62 ZZ结构域结合。Nt-Arg和合成配体与ZZ结构域的结合促进了p62的二硫键连接聚集和p62与LC3的相互作用，导致p62及其载体被传递到自噬体中。与其配体结合后，p62作为宏自噬的调节因子，诱导自噬体生物生成。通过这两种功能，细胞可以在自噬载体积累时激活p62并诱导选择性自噬。我们还提出，p62通过其结合Nt-Arg和其他N-降解子介导泛素蛋白酶体系统和自噬之间的相互作用。

  DOI：

  10.1038/s41467-017-00085-7
• 作为产物：
  描述：

  N-boc-(4-aminobutyl)biotinamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以90%的产率得到N-(4-氨基丁基)生物酰胺
  参考文献：
  名称：

  Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration

  摘要：

  Protein modifications in which the e-amino group of lysyl residues is incorporated into a 2-(omega-carboxy-ethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP: protein ratios is readily achieved using this strategy. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.009

文献信息

• Pyridinium derivatives and their use in determining connective tissue disorders in humans and animals
  申请人：SANDOZ LTD.

  公开号：EP0556152A1

  公开（公告）日：1993-08-18

  The invention relates to a process for producing pyridinoline and deoxypyridinoline crosslinks and derivatives thereof of formula (I) in which X, Y, Z, R₁, R₂, R₃, R₄,X₁ and X₂⊖ have meanings as given in the description and their use in determining connective tissue disorders in humans and animals.

  本发明涉及一种生产式 (I) 的吡啶啉和脱氧吡啶啉交联物及其衍生物的工艺 其中 X、Y、Z、R₁、R₂、R₃、R₄、X₁ 和 X₂⊖ 具有描述中给出的含义，以及它们在确定人类和动物结缔组织疾病中的用途。
• Synthesis of <i>N</i>,<i>N</i>‘-bis(Acrylamido)acetic Acid-Based T-Antigen Glycodendrimers and Their Mouse Monoclonal IgG Antibody Binding Properties
  作者：René Roy、Myung-Gi Baek、Kate Rittenhouse-Olson

  DOI：10.1021/ja002596w

  日期：2001.3.1

  Novel glycodendrimers based on N,N'-bis(acrylamido)acetic acid core with valencies between two and six were synthesized. The breast cancer-associated T-antigen carbohydrate marker, (beta -Gal-(1 -3)-alpha -GalNAc-OR), was then conjugated by (i) 1,4-conjugate addition of thiolated T-antigen to the N-acrylamido dendritic cores and by (ii) amide bond formation between an acid derivative of the T-antigen and the polyamino dendrimers. The protein-binding ability of these new glycodendrimers was fully demonstrated by turbidimetric analysis and by enzyme-linked immunosorbent assay (ELISA) using peanut lectin from Arachis hypogaea and a mouse monoclonal antibody (MAb) FAA-J11 (IgG3). When tested as inhibitors of binding between: MAb and a polymeric form of the T-antigen (T-antigen-co-polyacrylamide) used as a coating antigen, di(17), tetra- (20), hexa- (21.), and tetravalent (22) dendrimers showed IC50 values of 174, 19, 48, and 18 nM, respectively. Two tetramers showed 120- to similar to 128-fold increased inhibitory properties over the monovalent antigen 6 used as a standard (IC50 2.3 mM). Heterobifunctional glycodendrimer bearing a biotin probe was also prepared for cancer cell labeling.
• New methodology for the synthesis of 25-hydroxyvitamin D conjugates
  作者：Jonathan Grote、Susan Gayda

  DOI：10.1016/j.tetlet.2014.08.006

  日期：2014.10

  A new method for synthesizing regiospecific 3-position vitamin D conjugates is described. Reaction of either 25-dihydroxyvitamin D2 or 25-dihydroxyvitamin D3 with p-nitrophenylchloroformate resulted in conversion to the respective 3-p-nitrophenylcarbonates. Reaction of the p-nitrophenylcarbonates with amines produced the 3-carbamates in good yield. Careful selection of commercially available amines and non-acidic conditions made this pathway amenable to the preparation of fluorescent, chemiluminescent, or biotinylated conjugates. This strategy offers a general method for the preparation of vitamin D conjugates. (C) 2014 Elsevier Ltd. All rights reserved.
• US6175016B1
  申请人：——

  公开号：US6175016B1

  公开（公告）日：2001-01-16
• p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis
  作者：Hyunjoo Cha-Molstad、Ji Eun Yu、Zhiwei Feng、Su Hyun Lee、Jung Gi Kim、Peng Yang、Bitnara Han、Ki Woon Sung、Young Dong Yoo、Joonsung Hwang、Terry McGuire、Sang Mi Shim、Hyun Dong Song、Srinivasrao Ganipisetti、Nuozhou Wang、Jun Min Jang、Min Jae Lee、Seung Jun Kim、Kyung Ho Lee、Jin Tae Hong、Aaron Ciechanover、Inhee Mook-Jung、Kwang Pyo Kim、Xiang-Qun Xie、Yong Tae Kwon、Bo Yeon Kim

  DOI：10.1038/s41467-017-00085-7

  日期：——

  Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons.

  宏自噬介导了蛋白质和非蛋白质细胞成分的选择性降解。在这里，我们展示了N-末端规则途径调节宏自噬。在这种机制中，自噬适配器p62/SQSTM1/Sequestosome-1是一个N-识别蛋白，能结合类型1和类型2的N末端降解子（N-降解子），包括精氨酸（Nt-Arg）。这两种类型的N-降解子结合其ZZ结构域。通过三维建模，我们开发了合成配体与p62 ZZ结构域结合。Nt-Arg和合成配体与ZZ结构域的结合促进了p62的二硫键连接聚集和p62与LC3的相互作用，导致p62及其载体被传递到自噬体中。与其配体结合后，p62作为宏自噬的调节因子，诱导自噬体生物生成。通过这两种功能，细胞可以在自噬载体积累时激活p62并诱导选择性自噬。我们还提出，p62通过其结合Nt-Arg和其他N-降解子介导泛素蛋白酶体系统和自噬之间的相互作用。