3-((2-(tert-butoxycarbonylamino)ethyl)disulfanyl)propanoic acid | 485800-27-9

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: 3-((2-(tert-butoxycarbonylamino)ethyl)disulfanyl)propanoic acid
• 英文别名: 3-(2-tert-butoxycarbonylamino-ethyldisulfanyl)propionic acid；3-(2-tert-butoxycarbonylaminoethyldisulfanyl)propanoic acid；Boc-NH-ethyl-SS-propionic acid；3-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyldisulfanyl]propanoic acid
• CAS: 485800-27-9
• 化学式: C₁₀H₁₉NO₄S₂
• 分子量: 281.397
• InChiKey: CIJZYVBXQKYUFA-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于DMSO、DCM、DMF

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温、避光、干燥密封保存。

制备方法与用途

生物活性

Boc-NH-ethyl-SS-propionic acid 是一种可降解的 ADC 连接子，可用于合成抗体偶联药物 (ADC)。

靶点

Cleavable

体外研究

抗体偶联药物 (ADCs) 由通过 ADC 连接子连接到抗体上的 ADC 细胞毒物组成。

反应信息

• 作为反应物：
  描述：

  3-((2-(tert-butoxycarbonylamino)ethyl)disulfanyl)propanoic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 N-(1-amino-7-oxo-11,14-dioxa-3,4-dithia-8-azahexadecan-16-yl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
  参考文献：
  名称：

  Design, Synthesis and Preliminary Biological Evaluation of a Biotin-S-S-Phosphine Reagent

  摘要：

  生物素-S-S-膦化物被设计和合成，作为一种潜在的工具，用于研究O-GlcNAc修饰蛋白的蛋白质组学研究。该试剂的特点是通过二硫键连接的三芳基膦部分，允许选择性地与含叠氮的蛋白质结合，以及一个生物素部分，可以通过其对亲和素包被的固态珠子的强亲和性，实现轻松的分离。该试剂中的二硫键可以使得容易释放所结合的感兴趣的分子，这在单独使用生物素：亲和素对时难以实现，通过使用DTT还原试剂的二硫键。初步的体外生物学测定与带有和不带叠氮标记的细胞裂解物以及纯蛋白质Nup62一起进行，结果显示生物素-S-S-膦化物试剂对蛋白质的自由巯基具有高度反应性。当具有二硫键连接的分子工具应用于从其他物种中富集感兴趣的分子时，重要的是在使用StAUDinger连接反应之前使用彻底的烷基化阻断样品的自由巯基，以恢复该反应的生物正交性质。

  DOI：

  10.5012/bkcs.2014.35.2.383
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 氯仿 、 水 为溶剂， 生成 3-((2-(tert-butoxycarbonylamino)ethyl)disulfanyl)propanoic acid
  参考文献：
  名称：

  Metal Complex Mediated Conjugation of Peptides to Nucleus Targeting Acridine Orange: A Modular Concept for Dual-Modality Imaging Agents

  摘要：

  To target the nucleus of specific cells, trifunctional radiopharmaceuticals are required. We have synthesized acridine orange derivatives which comprise an imidazole-2-carbaldehyde function for coordination to the [Re(CO)(3)](+) or [(99)mTc(CO)(3)](+) core. Upon coordination, this aldehyde is activated and rapidly forms imines with amines from biological molecules. This metal-mediated imine formation allows for the conjugation of a nuclear targeting portion with a specific cell receptor binding function directly on the metal. With this concept, we have conjugated the acridine orange part to a bombesin peptide directly on the Tc-99m core and in one step. In addition, a linker containing an integrated disulfide has been coupled to bombesin. LC/MS study showed that the disulfide was reductively cleaved with a 60 min half-life time. This concept enables the combination of a nucleus targeting agent with a specific cell receptor molecule directly on the metal without the need of separate conjugation prior to labeling, thus, a modular approach. High uptake of the BBN conjugate into PC-3 cells was detected by fluorescence microscopy, whereas uptake into B16BL6 cells was negligible.

  DOI：

  10.1021/bc2000269

文献信息

• [EN] REAGENTS FOR REVERSIBLY TERMINATING PRIMER EXTENSION<br/>[FR] RÉACTIFS UTILISÉS POUR L'INTERRUPTION RÉVERSIBLE D'EXTENSION D'AMORCE
  申请人：BENNER STEVEN ALBERT

  公开号：WO2010110775A1

  公开（公告）日：2010-09-30

  This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions of matter that comprise triphosphates of modified 2'-deoxynucleosides and oligonucleotides that are formed when these are appended to the 3'-end of a primer, wherein said modifications comprise NH2 moiety attached to their 3'-hydroxyl group and a fluorescent species in a form of a tag affixed to the nucleobase via a linker that can be cleaved. Such compositions and their associated processes enable and improve the sequencing of oligonucleotides using a strategy of cyclic reversible termination, as outlined in US Patent 6,664,079. Most specifically, the invention concerns compositions of matter that are 5'-triphosphates of ribo- and 2'- deoxyribonucleosides carrying detectable tags and oligonucleotides that might be derived from them. The invention also concerns processes wherein a DNA polymerase, RNA polymerase, or reverse transcriptase synthesizes said oligonucleotides via addition of said triphosphates to a primer.

  这项发明涉及核酸化学领域，更具体地涉及包括改性2'-脱氧核苷酸三磷酸和寡核苷酸的物质组合的领域，当这些物质附加到引物的3'-末端时形成，其中这些改性包括连接到它们的3'-羟基的NH2基团和以可切割的方式通过连接器固定到核碱基上的荧光物种的标签。这种组合物及其相关的过程使得并改善了使用循环可逆终止策略进行寡核苷酸测序，正如美国专利6,664,079中所概述的那样。具体而言，该发明涉及的是包含可检测标签的核糖和2'-脱氧核糖核苷酸的5'-三磷酸和可能由它们衍生的寡核苷酸的物质组合。该发明还涉及DNA聚合酶、RNA聚合酶或逆转录酶通过将这些三磷酸添加到引物而合成所述寡核苷酸的过程。
• Ligands and libraries of ligands
  申请人：Wells Jim

  公开号：US20080261831A1

  公开（公告）日：2008-10-23

  The invention relates to variants of Target Biological Molecules (TBMs), such as proteins, peptides and other amino acid sequences that are modified to include cysteine residues at predetermined positions within the TBM. The position of amino acid residues within the TBM that are modified to be cysteine residues is selected for its proximity to ligand binding sites within the TBM. Once an amino acid residue, or the DNA encoding the residue, is modified to cysteine, the TBM linked to potential binding ligands by forming a covalent bond through the cysteine thiol (—SH) reactive group of the variant.

  本发明涉及靶生物分子（TBM）的变异体，例如蛋白质、肽和其他氨基酸序列，这些序列被修改以在TBM内的预定位置包括半胱氨酸残基。所选的氨基酸残基位置在TBM内被修改为半胱氨酸残基，是由于其靠近TBM内配体结合位点。一旦氨基酸残基或编码该残基的DNA被修改为半胱氨酸，TBM通过半胱氨酸巯基（—SH）反应基团形成共价键与潜在的结合配体相连。
• Methods of chemotype evolution
  申请人：Hansen Stig

  公开号：US10107798B2

  公开（公告）日：2018-10-23

  Herein is described a method to rapidly screen a large chemical space for a compound that binds to a target protein through an iterative fragment assembly approach that can be performed at low reagent cost and without requiring purification of the assembled product. The method employs a library of test ligands each of which comprise a ‘bait’ molecule, which is known from prior art or prior screening to have some intrinsic affinity for the target protein, and a test moiety.

  本文介绍了一种通过迭代片段组装方法快速筛选大量化学空间中与目标蛋白质结合的化合物的方法，该方法试剂成本低，无需对组装产物进行纯化。 该方法采用了一个测试配体库，每个配体都由一个 "诱饵 "分子和一个测试分子组成，"诱饵 "分子在现有技术或先前的筛选中已知对目标蛋白质具有某种内在亲和力。
• METHODS OF CHEMOTYPE EVOLUTION
  申请人：Sunesis Pharmaceuticals, Inc.

  公开号：EP2257637B1

  公开（公告）日：2015-09-23
• In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)
  作者：Huricha Baigude、Jie Su、Joshua McCarroll、Tariq M. Rana

  DOI：10.1021/ml4001003

  日期：2013.8.8

  RNA interference (RNAi) has considerable potential as a therapeutic strategy, but the development of efficient in vivo RNA delivery methods remains challenging. To this end, we designed and synthesized chemically modified interfering nanoparticles (iNOPs) composed of functionalized poly-L-lysine dendrimers modified with reducible spacers to facilitate release of small interfering RNAs (siRNAs) in vivo. We show that the novel siRNA-iNOP complexes mediate efficient gene-specific RNAi in cultured cells and in mice, where they display enhanced tissue-targeting capabilities. At a clinically feasible dose of 1 mg kg(-1), apolipoprotein B (apoB) siRNA-iNOP complexes achieved similar to 40-45% reduction of liver apoB mRNA and plasma apoB protein levels within 48 h of administration to mice, without apparent toxicity. Collectively, these findings demonstrate that siRNA delivery by the modified reducible iNOPs can provide a clinically significant and potentially tissue-specific new approach for RNAi therapy.