(2S)-2,3-bis[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]-N-[2-(1H-indol-3-yl)ethyl]propanamide | 1217891-29-6

• 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: (2S)-2,3-bis[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]-N-[2-(1H-indol-3-yl)ethyl]propanamide
• CAS: 1217891-29-6
• 化学式: C₃₃H₅₈N₁₂O₅
• 分子量: 702.901
• InChiKey: IOCJZBJBCRKOIB-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  50
• 可旋转键数：
  27
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  272
• 氢给体数：
  10
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Boc-Lys(2-chlorocarbobenzoxy)-OH 、 (2S)-2,3-bis[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]-N-[2-(1H-indol-3-yl)ethyl]propanamide 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以62.8%的产率得到
  参考文献：
  名称：

  [EN] DENDRIMERIC COMPOUNDS COMPRISING AMINO ACIDS, HYPERBRANCHED CORE COMPOUND, PROCESS FOR PREPARATION OF DENDRIMERIC COMPOUNDS COMPRISING AMINO ACIDS AND HYPERBRANCHED CORE COMPOUND, AND USE THEREOF
  [FR] COMPOSÉS DENDRIMÉRIQUES COMPRENANT DES ACIDES AMINÉS, COMPOSÉ COEUR HYPERRAMIFIÉ, PROCÉDÉ DE PRÉPARATION DE COMPOSÉS DENDRIMÉRIQUES COMPRENANT DES ACIDES AMINÉS ET UN COMPOSÉ COEUR HYPERRAMIFIÉ, ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2010033043A8
• 作为产物：
  描述：

  tetramethyl 3,3',3'',3'''-((3-((2-(1H-indol-3-yl)ethyl)amino)-3-oxopropane-1,2-diyl)bis(azanetriyl))(S)-tetrapropionate 、 乙二胺 以 甲醇 为溶剂， 反应 120.0h， 以92%的产率得到(2S)-2,3-bis[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]-N-[2-(1H-indol-3-yl)ethyl]propanamide
  参考文献：
  名称：

  Sap6, a secreted aspartyl proteinase, participates in maintenance the cell surface integrity of Candida albicans

  摘要：

  多形性物种白色念珠菌是人念珠菌病的主要病因。白色念珠菌分泌的天冬氨酸蛋白酶(Saps)由一组10个SAP基因编码,已被研究作为念珠菌病的毒力因子。然而,大多数Sap蛋白的生物学功能仍然不确定。在本研究中,我们采用了白色念珠菌和THP-1人单核细胞的共培养系统来探索Sap蛋白酶的致病作用和生物学功能。在37°C下共培养白色念珠菌株和THP-1人单核细胞1小时后,超过60%的THP-1吞噬的野生型和Δsap5白色念珠菌细胞正在发育长菌丝。然而,大约50%的THP-1吞噬的Δsap6白色念珠菌细胞正在产生短菌丝,并且在被THP-1细胞吞噬的Δsap6菌株中发现了更多的死白色念珠菌细胞(Δsap6菌株中约15%,而SC5314和Δsap5菌株中约2~2.5%)。免疫荧光染色证明,Sap6是THP-1吞噬作用下位于菌丝顶端的主要Sap蛋白。sap6缺失菌株(Δsap6,Δsap4/6和Δsap5/6)在含有刚果红的固体培养基上在25°C下生长较慢,并且在含有刚果红或SDS的培养基中在37°C下培养时生长缺陷加剧。此外,从Δsap6菌株分泌的蛋白更多,并且从Δsap6突变体提取的可溶于β-巯基乙醇(β-ME)的表面蛋白比从野生型菌株提取的更丰富,其中包括质膜蛋白(Pma1p)、内质网伴侣蛋白(Kar2p)、蛋白质运输相关蛋白(Arf1p)、细胞骨架蛋白(Act1)和线粒体外膜蛋白(孔蛋白1)。此外,sap6缺失菌株的细胞表面可及性增加。从这些结果中,我们推测Δsap6白色念珠菌菌株的细胞表层结构存在缺陷。这可能导致β-ME更容易接近二硫键连接的细胞表面成分,并且可能削弱Δsap6菌株在遇到THP-1细胞的吞噬作用时的抵抗力。Sap6蛋白在维持细胞表面完整性方面显示出重要的作用。

  DOI：

  10.1186/1423-0127-20-101

文献信息

• DENDRIMERIC COMPOUNDS COMPRISING AMINO ACIDS, HYPERBRANCHED CORE COMPOUND, PROCESS FOR PREPARATION OF DENDRIMERIC COMPOUNDS COMPRISING AMINO ACIDS AND HYPERBRANCHED CORE COMPOUND, AND USE THEREOF
  申请人：Lipkowska Zofia

  公开号：US20110152175A1

  公开（公告）日：2011-06-23

  The invention provides dendrimeric compounds of the formula 1 comprising amino acids, wherein n is an integer of 1-4, T is an alkylidene —(CH2)2CONH(CH2)2- group, R2 is an —NH2 group or a moiety of a primary organic amine, and P is an amino acid and/or peptide moiety, wherein at least one hydrogen atom of at least one amino group is optionally replaced by a protective group, and a hyperbranched core compound of the formula 3, wherein T and R2 are as defined above. The invention provides also a process for the preparation of a dendrimeric compound and a hyperbranched core, wherein the process employs addition reactions of alkyl acrylate and a basic amino acid, and use of a hyperbranched core for the preparation of a dendrimeric compound comprising amino acids. The invention provides also use of dendrimeric compounds for the preparation of the medicament for inhibiting growth of bacterial cells, fungi and tumor cells.

  本发明提供了公式1的树状化合物，其中包括氨基酸，其中n为1-4的整数，T为烷基亚甲基—(CH2)2CONH(CH2)2-基团，R2为—NH2基团或初级有机胺的基团，P为氨基酸和/或肽的基团，其中至少一个氨基团的至少一个氢原子可选择性地被保护基替代，以及公式3的高分支核心化合物，其中T和R2如上所定义。本发明还提供了制备树状化合物和高分支核心的方法，其中该方法采用烷基丙烯酸酯和碱性氨基酸的加成反应，并使用高分支核心制备包含氨基酸的树状化合物。本发明还提供了使用树状化合物制备抑制细菌细胞、真菌和肿瘤细胞生长的药物的用途。
• US8541365B2
  申请人：——

  公开号：US8541365B2

  公开（公告）日：2013-09-24
• Sap6, a secreted aspartyl proteinase, participates in maintenance the cell surface integrity of Candida albicans
  作者：Leh-Miauh Buu、Yee-Chun Chen

  DOI：10.1186/1423-0127-20-101

  日期：2013.12

  The polymorphic species Candida albicans is the major cause of candidiasis in humans. The secreted aspartyl proteinases (Saps) of C. albicans, encoded by a family of 10 SAP genes, have been investigated as the virulent factors during candidiasis. However, the biological functions of most Sap proteins are still uncertain. In this study, we applied co-culture system of C. albicans and THP-1 human monocytes to explore the pathogenic roles and biological functions of Sap proteinases. After 1 hr of co-culture of C. albicans strains and THP-1 human monocytes at 37°C, more than 60% of the THP-1-engulfed wild type and Δsap5 Candida cells were developing long hyphae. However, about 50% of THP-1-engulfed Δsap6 Candida cells were generating short hyphae, and more dead Candida cells were found in Δsap6 strain that was ingested by THP-1 cells (about 15% in Δsap6 strain vs. 2 ~ 2.5% in SC5314 and Δsap5 strains). The immunofluorescence staining demonstrated that the Sap6 is the major hyphal tip located Sap protein under THP-1 phagocytosis. The sap6-deleted strains (Δsap6, Δsap4/6, and Δsap5/6) appeared slower growth on Congo red containing solid medium at 25°C, and the growth defect was exacerbated when cultured at 37°C in Congo red or SDS containing medium. In addition, more proteins were secreted from Δsap6 strain and the β-mercaptoethanol (β-ME) extractable surface proteins from Δsap6 mutant were more abundant than that of extracted from wild type strain, which included the plasma membrane protein (Pma1p), the ER-chaperone protein (Kar2p), the protein transport-related protein (Arf1p), the cytoskeleton protein (Act1), and the mitochondrial outer membrane protein (porin 1). Moreover, the cell surface accessibility was increased in sap6-deleted strains. From these results, we speculated that the cell surface constitution of C. albicans Δsap6 strain was defect. This may cause the more accessible of β-ME to disulfide-bridged cell surface components and may weaken the resistance of Δsap6 strain encountering phagocytosis of THP-1 cells. Sap6 protein displays a significant function involving in maintenance the cell surface integrity.

  多形性物种白色念珠菌是人念珠菌病的主要病因。白色念珠菌分泌的天冬氨酸蛋白酶(Saps)由一组10个SAP基因编码,已被研究作为念珠菌病的毒力因子。然而,大多数Sap蛋白的生物学功能仍然不确定。在本研究中,我们采用了白色念珠菌和THP-1人单核细胞的共培养系统来探索Sap蛋白酶的致病作用和生物学功能。在37°C下共培养白色念珠菌株和THP-1人单核细胞1小时后,超过60%的THP-1吞噬的野生型和Δsap5白色念珠菌细胞正在发育长菌丝。然而,大约50%的THP-1吞噬的Δsap6白色念珠菌细胞正在产生短菌丝,并且在被THP-1细胞吞噬的Δsap6菌株中发现了更多的死白色念珠菌细胞(Δsap6菌株中约15%,而SC5314和Δsap5菌株中约2~2.5%)。免疫荧光染色证明,Sap6是THP-1吞噬作用下位于菌丝顶端的主要Sap蛋白。sap6缺失菌株(Δsap6,Δsap4/6和Δsap5/6)在含有刚果红的固体培养基上在25°C下生长较慢,并且在含有刚果红或SDS的培养基中在37°C下培养时生长缺陷加剧。此外,从Δsap6菌株分泌的蛋白更多,并且从Δsap6突变体提取的可溶于β-巯基乙醇(β-ME)的表面蛋白比从野生型菌株提取的更丰富,其中包括质膜蛋白(Pma1p)、内质网伴侣蛋白(Kar2p)、蛋白质运输相关蛋白(Arf1p)、细胞骨架蛋白(Act1)和线粒体外膜蛋白(孔蛋白1)。此外,sap6缺失菌株的细胞表面可及性增加。从这些结果中,我们推测Δsap6白色念珠菌菌株的细胞表层结构存在缺陷。这可能导致β-ME更容易接近二硫键连接的细胞表面成分,并且可能削弱Δsap6菌株在遇到THP-1细胞的吞噬作用时的抵抗力。Sap6蛋白在维持细胞表面完整性方面显示出重要的作用。
• [EN] DENDRIMERIC COMPOUNDS COMPRISING AMINO ACIDS, HYPERBRANCHED CORE COMPOUND, PROCESS FOR PREPARATION OF DENDRIMERIC COMPOUNDS COMPRISING AMINO ACIDS AND HYPERBRANCHED CORE COMPOUND, AND USE THEREOF<br/>[FR] COMPOSÉS DENDRIMÉRIQUES COMPRENANT DES ACIDES AMINÉS, COMPOSÉ COEUR HYPERRAMIFIÉ, PROCÉDÉ DE PRÉPARATION DE COMPOSÉS DENDRIMÉRIQUES COMPRENANT DES ACIDES AMINÉS ET UN COMPOSÉ COEUR HYPERRAMIFIÉ, ET LEURS UTILISATIONS
  申请人：INST CHEMII ORGANICZNEJ POLSKA

  公开号：WO2010033043A8

  公开（公告）日：2010-05-14