N,N'-二(3-马来酰亚胺丙酰基)-2-羟基-1,3-丙烷二胺 | 115388-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: N,N'-二(3-马来酰亚胺丙酰基)-2-羟基-1,3-丙烷二胺
• 中文别名: N,N′-双(3-马来酰亚胺丙酰基)-2-羟基-1,3-丙二胺
• 英文名称: N,N'-bis(3-maleimidopropionyl)-2-hydroxy-1,3-propanediamine
• 英文别名: N,N'-Bis(3-maleimidepropionyl)-2-hydroxy-1,3-propanediamine；3-(2,5-dioxopyrrol-1-yl)-N-[3-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]-2-hydroxypropyl]propanamide
• CAS: 115388-98-2
• 化学式: C₁₇H₂₀N₄O₇
• 分子量: 392.368
• InChiKey: IAFNXCHKPVIFPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(S)-2-((S)-6-((R)-4-Amino-2-hydroxy-butylamino)-2-{2-[(2S,3R)-2-((R)-2-amino-3-mercapto-propionylamino)-3-hydroxy-butyrylamino]-acetylamino}-hexanoylamino)-3-(1H-imidazol-4-yl)-propionylamino]-acetic acid 、 N,N'-二(3-马来酰亚胺丙酰基)-2-羟基-1,3-丙烷二胺 在 phosphate buffer 作用下， 生成
  参考文献：
  名称：

  Synthesis of Reagents for the Construction of Hypusine and Deoxyhypusine Peptides and Their Application as Peptidic Antigens

  摘要：

  Two new synthetic methods which allow access to (2S)-deoxyhypusine, natural (2S,9R)hypusine, (2S,SS)-hypusine, and deoxyhypusine- and hypusine-containing peptides are described. The methods involve both the construction of a deoxyhypusine reagent in which the alpha-nitrogen protecting group is orthogonal to the N-7 and N-12 protecting groups and an alternate synthesis of our previous hypusine reagent, a synthesis which provides for better stereochemical control at C-9. Synthetic hypusine and deoxyhypusine can be generated from these reagents. The hypusine-containing hexapeptide (Cys-Thr-Gly-Hpu-His-Gly) is conjugated to ovalbumin (OVA), keyhole limpet hemocyanin (KLH), and a bis-maleimide; KLH conjugates are also made with the deoxyhypusine- and lysine-containing hexapeptides. Monoclonal antibodies are generated to the hypusine-containing hexapeptide-OVA conjugate in mice. These are isolated and screened against the hypusine-containing hexapeptide-KLH and hypusine-containing hexapeptide-bis-maleimide conjugates, as well as against the deoxyhypusine-containing and lysine-containing hexapeptide-KLH conjugates. These antibodies may be useful in localizing intracellular hypusine-containing peptides as well as peptides containing hypusine analogues.

  DOI：

  10.1021/jm980389p

文献信息

• Protein Carrier-Linked Prodrugs
  申请人：Hersel Ulrich

  公开号：US20140323402A1

  公开（公告）日：2014-10-30

  The present invention relates to water-soluble protein carrier-linked prodrugs wherein the protein carrier comprises an amino acid sequence consisting of at least 100 amino acid residues forming random coil conformation and comprising alanine, serine and proline residues. It further relates to pharmaceutical compositions comprising said water-soluble protein carrier-linked prodrugs, their use as a medicament as well as methods of treatment and administration.

  本发明涉及水溶性蛋白质载体连接的前药，其中蛋白质载体包括由至少100个氨基酸残基组成的氨基酸序列，形成随机卷曲构象，并包括丙氨酸，丝氨酸和丙氨酸残基。它还涉及包含所述水溶性蛋白质载体连接的前药的制药组合物，它们作为药物的使用以及治疗和管理的方法。
• Tris-maleimido compounds as intermediates in trifunctional antibody synthesis
  申请人：HYBRITECH INCORPORATED

  公开号：EP0446071A2

  公开（公告）日：1991-09-11

  The present invention is directed to a compound for use as an intermediate in the production of novel trifunctional antibody-like compounds. More particularly, the present invention is directed to a compound of the formula : wherein X is wherein k =1 or 0 ; wherein Z is -0-, or -NH-; wherein s = 1 or 0; wherein n = 1 or 0 ; wherein q = 1 or 0; wherein Y is -S-S-, -O-, or -NH-; wherein Y' is -S-S-, -O-, or -NH-; wherein p or m may be the same or different and are integers ranging from 0 to 20 with the provisos that when n = 0, the sum of m and p is an integer ranging from 1 to 20, whereas when n = 1, p and m are each an integer that is at least 1 and the sum of p and m is an integer ranging from 2 to 20 ; wherein R1 is straight or branched chain lower alkyl having from 1 to 6 carbon atoms or lower alkoxy having from 1-6 carbon atoms ; and wherein R2 is hydrogen, phenyl, -COOH, or straight or branched chain lower alkyl having from 1-6 carbon atoms, with the proviso that the lower alkyl moiety may be mono substituted by -NH2, -OH, or -COOH. The compound of the present invention is useful as a trivalent coupling agent for linking Fab'-like fragments to form both bifunctional and trifunctional antibody-like compounds.

  本发明涉及一种用于生产新型三官能抗体样化合物的中间体的化合物。更具体地说，本发明涉及一种式......的化合物： 其中 X 是 其中 k =1 或 0 ；其中 Z 是 -0-，或-NH-； 其中 s = 1 或 0； 其中 n = 1 或 0； 其中 q = 1 或 0； 其中 Y 是 -S-S-、 其中Y'是-S-S-、-O-或-NH-； 其中Y'是-S-S-、-O-或-NH-、 -其中 p 或 m 可以相同或不同，并且是 0 至 20 之间的整数，但当 n = 0 时，m 与 p 之和是 1 至 20 之间的整数，而当 n = 1 时，p 和 m 分别是至少为 1 的整数，并且 p 与 m 之和是 2 至 20 之间的整数；其中 R1 是具有 1-6 个碳原子的直链或支链低级烷基或具有 1-6 个碳原子的低级烷氧基；其中 R2 是氢、苯基、-COOH 或具有 1-6 个碳原子的直链或支链低级烷基，但低级烷基可被-NH2、-OH 或-COOH 单取代。 本发明的化合物可作为三价偶联剂，用于连接 Fab'-like 片段，形成双官能和三官能抗体样化合物。
• Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent
  申请人：HYBRITECH INCORPORATED

  公开号：EP0453082A1

  公开（公告）日：1991-10-23

  The present invention has multiple aspects. In its first aspect the present invention is directed to a trifunctional antibody-like compound that has tissue, organ, cell or molecule specificity and which is capable of being bifunctional when immobilized, via binding, at the tissue, organ, cell or molecule for which it has specificity. In particular, the present invention is directed to a trifunctional antibody-like compound of Formula I:    wherein L is one or two moieties for cross-linking F₁ab′, F₂ab′ and F₃ab′;    wherein F₁ab′ is an Fab′-like fragment of a polyclonal or monoclonal antibody having specificity for an antigen expressed by the organ, tissue, cell or molecule of interest;    wherein F₂ab′ is an Fab′-like fragment of a polyclonal or monoclonal antibody having the same specificity as F₁ab′, or having specificity either for a different antigen expressed by the organ, tissue, cell, or molecule of interest, or for a diagnostic or therapeutic agent; and    wherein F₃ab′ is an Fab′-like fragment of a polyclonal or monoclonal antibody having specificity for a diagnostic or therapeutic agent; or    wherein F₂ab′ and F₃ab′ have specificity for a receptor/receptor complex and accessory molecule on the surface of a T-cell. The compound of the present invention has utility as a pharmaceutical agent. Various methods for treating and diagnosing a disease are also presented.

  本发明涉及多个方面。第一方面，本发明涉及一种三官能团抗体样化合物，它具有组织、器官、细胞或分子特异性，当通过结合固定在其具有特异性的组织、器官、细胞或分子上时，能够具有双官能团。本发明尤其涉及式 I 的三官能团抗体样化合物： 其中 L 是用于交联 F₁ab′、F₂ab′ 和 F₃ab′ 的一个或两个分子； 其中 F₁ab′ 是多克隆或单克隆抗体的 Fab′ 样片段，对相关器官、组织、细胞或分子表达的抗原具有特异性； 其中，F₂ab′是多克隆或单克隆抗体的 Fab′样片段，该抗体具有与 F₁ab′ 相同的特异性，或对相关器官、组织、细胞或分子表达的不同抗原或诊断或治疗剂具有特异性；以及 其中 F₃ab′ 是对诊断或治疗剂具有特异性的多克隆或单克隆抗体的 Fab′ 样片段；或 其中 F₂ab′ 和 F₃ab′ 对 T 细胞表面的受体/受体复合物和附属分子具有特异性。 本发明的化合物可用作药剂。还介绍了治疗和诊断疾病的各种方法。
• Polymeric prodrugs
  申请人：Complex Biosystems GmbH

  公开号：EP2087910A2

  公开（公告）日：2009-08-12

  The present invention relates to a polymeric cascade prodrug comprising: an amine containing biologically active moiety, a polymeric carrier, a masking group having at least one nucleophile and being distinct from the carrier, wherein the prodrug is predominantly non-enzymatically cleavable.

  本发明涉及一种聚合级联原药，包括：含生物活性分子的胺、聚合载体、至少有一个亲核且与载体不同的掩蔽基团，其中原药主要是非酶可裂解的。
• Osteocalcin as a treatment for cognitive disorders
  申请人：THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

  公开号：US10052364B2

  公开（公告）日：2018-08-21

  Methods and compositions for treating or preventing cognitive disorders in mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-1B signaling pathway involving gamma-carboxylase and osteocalcin, e.g., by administration of undercarboxylated/uncarboxylated osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, cognitive loss due to neurodegeneration associated with aging, anxiety, depression, memory loss, learning difficulties, and cognitive disorders associated with food deprivation during pregnancy.

  本研究提供了治疗或预防哺乳动物（最好是人类）认知障碍的方法和组合物。这些方法通常涉及调节 OST-PTP 信号通路或涉及γ-羧化酶和骨钙素的 PTP-1B 信号通路，例如通过施用羧化不足/未羧化的骨钙素。可通过这些方法治疗的疾病包括但不限于与衰老相关的神经变性导致的认知功能丧失、焦虑、抑郁、记忆力减退、学习困难以及与孕期食物匮乏相关的认知障碍。