(3S)-3-羧基-6-[[(1,1-二甲基乙氧基)羰基]氨基]-10,10-二甲基-8-氧代-9-氧杂-2,5,7-三氮杂十一碳-5-烯酸 1-(9H-芴-9-基甲基)酯 | 313232-63-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (3S)-3-羧基-6-[[(1,1-二甲基乙氧基)羰基]氨基]-10,10-二甲基-8-氧代-9-氧杂-2,5,7-三氮杂十一碳-5-烯酸 1-(9H-芴-9-基甲基)酯
• 中文别名: (3S)-3-羧基-6-[[(1,1-二甲基乙氧基)羰基]氨基]-10,10-二甲基-8-氧代-9-氧杂-2,5,7-三氮杂十一碳-5-烯酸1-(9H-芴-9-基甲基)酯；(S)-2-((((9H-芴-9-基)甲氧基)羰基)氨基)-3-((2,2,10,10-四甲基-4,8-二氧代-3,9-二氧杂-5,7-二氮杂-6-亚基)氨基)丙酸
• 英文名称: Fmoc-Agp(Boc)2
• 英文别名: Fmoc-Agp(Boc)2-OH；(2S)-3-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 313232-63-2
• 化学式: C₂₉H₃₆N₄O₈
• 分子量: 568.627
• InChiKey: KWUNKMXCVKSAEL-QFIPXVFZSA-N

物化性质

• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  9

安全信息

• WGK Germany：
  2
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (3S)-3-羧基-6-[[(1,1-二甲基乙氧基)羰基]氨基]-10,10-二甲基-8-氧代-9-氧杂-2,5,7-三氮杂十一碳-5-烯酸 1-(9H-芴-9-基甲基)酯 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 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.17h， 生成 tert-butyl (12S,E)-6,12-bis((tert-butoxycarbonyl)amino)-9-((3-(4-((3-(2,3-difluoro-4-methoxyphenyl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-ethylbenzamido)propyl)carbamoyl)-2,2-dimethyl-4,11-dioxo-3-oxa-5,7,10-triazapentadec-5-en-1 5-oate
  参考文献：
  名称：

  [EN] NOVEL IMIDAZOPYRAZINE DERIVATIVES AS ANTIBACTERIALS
  [FR] NOUVEAUX DÉRIVÉS D'IMIDAZOPYRAZINE EN TANT QU'ANTIBACTÉRIENS

  摘要：

  这项发明提供了具有通式（I）的新型咪唑吡嗪衍生物，其中R1至R11如本文所述，并其药学上可接受的盐。还提供了包括这些化合物的药物组合物、制造这些化合物的方法以及将这些化合物用作药物的方法，特别是将这些化合物用作抗生素治疗或预防细菌感染及相关疾病的方法。

  公开号：

  WO2020126953A1
• 作为产物：
  描述：

  、 1,3-二-BOC-2-(三氟甲基磺酰)胍 在 N-甲基-N-(三甲基硅烷基)三氟乙酰胺 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到(3S)-3-羧基-6-[[(1,1-二甲基乙氧基)羰基]氨基]-10,10-二甲基-8-氧代-9-氧杂-2,5,7-三氮杂十一碳-5-烯酸 1-(9H-芴-9-基甲基)酯
  参考文献：
  名称：

  Helix formation and capping energetics of arginine analogs with varying side chain length

  摘要：

  Arginine (Arg) has been used for recognizing negatively charged biological molecules, cell penetration, and oligosaccharide mass signal enhancement. The versatility of Arg has inspired the need to develop Arg analogs and to research the structural effects of incorporating Arg analogs. Accordingly, we investigated the effect of Arg side chain length on helix formation by studying 12 Ala-based peptides containing the Arg analogs (S)-2-amino-6-guanidino-hexanoic acid (Agh), (S)-2-amino-4-guanidinobutyric acid (Agb), and (S)-2-amino-3-guanidinopropionic acid (Agp). Solid phase guanidinylation with orthogonal protection strategies was necessary to synthesize Agb- and Agp-containing peptides using Fmoc-based chemistry. The fraction helix for the peptides was determined by circular dichroism spectroscopy, and used to derive the statistical mechanical parameters and energetics for N-capping, C-capping, and helix propagation (propensity). All four Arg analogs were unfavorable for N-capping. The C-cap parameter followed the trend Agp < Agb < Arg < Agh, showing more favorable C-cap energetics with increasing side chain length. In contrast, helix propensity followed the trend Agp < Agb < Arg > Agh, highlighting the uniqueness of the Arg side chain length in helix formation. Molecular mechanics calculations and a survey on protein structures were consistent with the experimental results. Furthermore, calculations and survey both showed that the g- conformation for the chi(1) dihedral was present for the first two residues at the N-terminus of helices, but not favored in the center or C-terminus of helices due to sterics. These results should serve as the foundation for developing Arg-related bioactive compounds and technologies.

  DOI：

  10.1007/s00726-011-1064-2

文献信息

• A Peptidomimetic Fluorescent Probe to Detect the Trypsin β2 Subunit of the Human 20S Proteasome
  作者：Magdalena Wysocka、Anita Romanowska、Natalia Gruba、Michalina Michalska、Artur Giełdoń、Adam Lesner

  DOI：10.3390/ijms21072396

  日期：——

  human proteasome. After deconvolution of a library comprising nearly 6000 compounds composed of peg substituted diaminopropionic acid DAPEG building blocks, the sequence ABZ-Dap(O2(Cbz))-Dap(GO1)-Dap(O2(Cbz))-Arg-ANB-NH2, where ABZ is 2-aminobenzoic acid, and ANB- 5 amino 2- nitro benzoic acid was selected. Its cleavage followed sigmoidal kinetics, characteristic for allosteric enzymes, with Km = 3.22

  这项工作描述了对20S人蛋白酶体的胰蛋白酶样（β2）亚基特异的拟肽荧光底物的化学合成，组合选择和酶促评估。在对包含近6000种由聚乙二醇取代的二氨基丙酸DAPEG结构单元组成的化合物的文库进行反卷积后，序列ABZ-Dap（O2（Cbz））-Dap（GO1）-Dap（O2（Cbz））-Arg-ANB-NH2其中ABZ是2-氨基苯甲酸，并且选择了ANB-5氨基2-硝基苯甲酸。其裂解遵循变构酶特征的S形动力学，Km = 3.22±0.02μM，kcat = 245 s-1，kcat / Km = 7.61×107 M-1 s-1。当将20S人蛋白酶体的β2亚基的选择性抑制剂添加到反应体系中时，该过程实际上停止了。底物的滴定导致减少的蛋白酶体20S量产生高达10-11 M的线性信号。使用这种底物，我们从癌症患者膀胱中采集的人尿液样品中检测到人蛋白酶体20S。该观察结果可用于这种严重疾病的非侵入性诊断。
• Broad-spectrum activity of membranolytic cationic macrocyclic peptides against multi-drug resistant bacteria and fungi
  作者：Sandeep Lohan、Anastasia G. Konshina、Rakesh K. Tiwari、Roman G. Efremov、Innokentiy Maslennikov、Keykavous Parang

  DOI：10.1016/j.ejps.2024.106776

  日期：2024.6

  Antimicrobial peptides (AMPs) are drawing considerable attention as promising antibiotic alternative candidates to combat MDR bacterial and fungal infections. Herein, we present a series of small amphiphilic membrane-active cyclic peptides composed, in part, of various nongenetically encoded hydrophilic and hydrophobic amino acids. Notably, lead cyclic peptides and showed broad-spectrum activity against drug-resistant

  由于治疗选择有限，多重耐药（MDR）菌株的出现给微生物感染的治疗带来了严重问题。抗菌肽（AMP）作为对抗多重耐药细菌和真菌感染的有前景的抗生素替代候选物而受到广泛关注。在此，我们提出了一系列小的两亲性膜活性环肽，部分由各种非遗传编码的亲水性和疏水性氨基酸组成。值得注意的是，先导环肽对耐药革兰氏阳性菌（MIC = 1.5–6.2 µg/mL）和革兰氏阴性菌（MIC = 12.5–25 µg/mL）和真菌（MIC = 3.1）表现出广谱活性。 –12.5 微克/毫升）。此外，先导肽表现出与标准抗生素相当的显着抗生物膜作用。溶血 (HC = 230 µg/mL) 和细胞毒性（100 µg/mL 对四种不同哺乳动物细胞的细胞活力 > 70%）测定结果表明，对微生物的选择性致死作用优于对哺乳动物细胞的选择性致死作用。钙黄绿素染料渗漏实验证实了 和 的膜溶解作用，并通过扫描电子显微镜进一步证实。通过采用核磁共振
• [EN] NOVEL IMIDAZOPYRAZINE DERIVATIVES AS ANTIBACTERIALS<br/>[FR] NOUVEAUX DÉRIVÉS D'IMIDAZOPYRAZINE EN TANT QU'ANTIBACTÉRIENS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2020126953A1

  公开（公告）日：2020-06-25

  The invention provides novel imidazopyrazine derivatives having general formula (I), wherein R1 to R11 are as described herein, and pharmaceutically acceptable salts thereof. Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and related diseases.

  这项发明提供了具有通式（I）的新型咪唑吡嗪衍生物，其中R1至R11如本文所述，并其药学上可接受的盐。还提供了包括这些化合物的药物组合物、制造这些化合物的方法以及将这些化合物用作药物的方法，特别是将这些化合物用作抗生素治疗或预防细菌感染及相关疾病的方法。
• Helix formation and capping energetics of arginine analogs with varying side chain length
  作者：Richard P. Cheng、Yi-Jen Weng、Wei-Ren Wang、Marc J. Koyack、Yuta Suzuki、Cheng-Hsun Wu、Po-An Yang、Hao-Chun Hsu、Hsiou-Ting Kuo、Prashant Girinath、Chun-Jen Fang

  DOI：10.1007/s00726-011-1064-2

  日期：2012.7

  Arginine (Arg) has been used for recognizing negatively charged biological molecules, cell penetration, and oligosaccharide mass signal enhancement. The versatility of Arg has inspired the need to develop Arg analogs and to research the structural effects of incorporating Arg analogs. Accordingly, we investigated the effect of Arg side chain length on helix formation by studying 12 Ala-based peptides containing the Arg analogs (S)-2-amino-6-guanidino-hexanoic acid (Agh), (S)-2-amino-4-guanidinobutyric acid (Agb), and (S)-2-amino-3-guanidinopropionic acid (Agp). Solid phase guanidinylation with orthogonal protection strategies was necessary to synthesize Agb- and Agp-containing peptides using Fmoc-based chemistry. The fraction helix for the peptides was determined by circular dichroism spectroscopy, and used to derive the statistical mechanical parameters and energetics for N-capping, C-capping, and helix propagation (propensity). All four Arg analogs were unfavorable for N-capping. The C-cap parameter followed the trend Agp < Agb < Arg < Agh, showing more favorable C-cap energetics with increasing side chain length. In contrast, helix propensity followed the trend Agp < Agb < Arg > Agh, highlighting the uniqueness of the Arg side chain length in helix formation. Molecular mechanics calculations and a survey on protein structures were consistent with the experimental results. Furthermore, calculations and survey both showed that the g- conformation for the chi(1) dihedral was present for the first two residues at the N-terminus of helices, but not favored in the center or C-terminus of helices due to sterics. These results should serve as the foundation for developing Arg-related bioactive compounds and technologies.