N1-benzyl-(2S)-2-amino-5-amino(imino)methylaminopentanamide | 37574-72-4

• 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: N1-benzyl-(2S)-2-amino-5-amino(imino)methylaminopentanamide
• 英文别名: L-arginine benzylamide；L-Arg-NHBzl；(2S)-2-amino-N-benzyl-5-(diaminomethylideneamino)pentanamide
• CAS: 37574-72-4
• 化学式: C₁₃H₂₁N₅O
• 分子量: 263.343
• InChiKey: VRXSUYRLBOIZPI-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N1-benzyl-(2S)-2-amino-5-amino(imino)methylaminopentanamide 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 L-arginyl-L-4,4'-biphenylalanyl-L-arginine benzylamide
  参考文献：
  名称：

  Albumin Binding of Short Cationic Antimicrobial Micropeptides and Its Influence on the in Vitro Bactericidal Effect

  摘要：

  The interactions between a range of small cationic antibacterial tripeptides and bovine and human serum albumin in a buffered aqueous solution at 25 degrees C have been studied using isothermal titration calorimetry. Results from the binding study indicate a single binding site on albumin with a dissociation constant between 4.3 and 22.2 mu M for the different peptides. In a theoretical mouse model, a dissociation constant in this range corresponds to 95% albumin binding. The effect of this albumin interaction on the antibacterial capacity of the peptides against Staphylococcus aureus, strain ATCC 25923 was studied by including albumin in the assays at a 0.55 mM concentration. Presence of albumin induced a 10-fold increase of the minimal inhibitory concentration for the bulk of the peptides. Albumin itself has no effect on the bacterial growth and this increase is entirely ascribed to a strong competing protein binding. Collectively these results indicate that these antibacterial peptides do bind to albumin and that this binding strongly reduces the effective concentration of peptides available to combat bacteria.

  DOI：

  10.1021/jm0703542
• 作为产物：
  描述：

  N-Boc-L-精氨酸 在 endo-N-Hydroxy-5-norbornene-2,3-dicarboximide 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N1-benzyl-(2S)-2-amino-5-amino(imino)methylaminopentanamide
  参考文献：
  名称：

  基于烷基化组氨酸的短阳离子抗真菌肽：合成，生物学评估和机理研究†

  摘要：

  当前临床上使用的抗真菌剂具有几个缺点，这些缺点迫切需要开发具有异常作用机理的新的抗真菌剂。在这种情况下，抗真菌肽（AFP）通过提供全系列的高选择性和无毒药物，为药物设计开辟了新的前景。在这里，我们报告了新型短AFP的发展，合成了两个基于三肽的化合物，称为His（2-烷基）-Arg-Lys（系列I）和His（2-烷基）-Arg-Arg（系列II） ）。发现II系列肽对新型隐球菌有选择性的活性，而一些肽对其他真菌菌株如白色念珠菌，假丝酵母，假丝酵母，表现出令人鼓舞的活性。黑曲霉和克雷索菌。使用Hek-293和HeLa细胞对活性化合物进行了细胞毒性实验，这些细胞在最高测试浓度下均表现出微不足道的细胞毒性作用。此外，使用TEM分析对最有效的肽进行了机理研究。用最有效的肽处理了两组模仿微生物膜和哺乳动物膜的SUV。发现该研究的结果与微生物和哺乳动物细胞膜组成之间的差异有关的抗真菌活性是完美的佐证，从

  DOI：

  10.1039/c6ra05883c

文献信息

• Modified histidine containing amphipathic ultrashort antifungal peptide, His[2-p-(n-butyl)phenyl]-Trp-Arg-OMe exhibits potent anticryptococcal activity
  作者：Krishna K. Sharma、Ravikant Ravi、Indresh Kumar Maurya、Akshay Kapadia、Shabana I. Khan、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.1016/j.ejmech.2021.113635

  日期：2021.11

  10 μg/mL. Peptide 14f act by nuclear fragmentation, membranes permeabilization, disruption and pore formations in the microbial cells as determined by the mechanistic studies employing Trp-quenching, CLSM, SEM, and HR-TEM. The amalgamation of short sequence, presence of appropriate aryl group on l-histidine, potent anticryptococcal activity, no cytotoxicity, and detailed mechanistic studies directed

  为了寻求基于超短肽的抗真菌剂，报道了一种新的结构类别 His(2-aryl)-Trp-Arg。在 His-Trp-Arg 支架上研究了结构变化，以证明电荷和亲脂性对生物活性的影响。组氨酸咪唑上芳基部分的存在和大小调节了整体两亲性特征和生物活性。肽对新型隐球菌的IC 50为 0.37–9.66 μg/mL 。肽14f [His(2- p- ( n-丁基)苯基)-Trp-Arg-OMe] 表现出 与两性霉素 B 相关的两倍效力 (IC 50 = 0.37 μg/mL, MIC = 0.63 μg/mL)任何高达 10 μg/mL 的细胞毒性作用。肽14f通过使用 Trp 淬灭、CLSM、SEM 和 HR-TEM 的机理研究确定的微生物细胞中的核碎裂、膜透化、破坏和孔形成起作用。短序列的合并、l-组氨酸上存在适当的芳基、有效的抗隐球菌活性、无细胞毒性以及旨在将14f鉴定为新的抗真菌结构先导物的详细机制研究。
• Synthesis and antimicrobial activities of His(2-aryl)-Arg and Trp-His(2-aryl) classes of dipeptidomimetics
  作者：Amit Mahindra、Krishna K. Sharma、Dinesh Rathore、Shabana. I. Khan、Melissa R. Jacob、Rahul Jain

  DOI：10.1039/c4md00041b

  日期：——

  In this communication, we report the design, synthesis andin vitroantimicrobial activity of ultra short peptidomimetics.

  在这份通讯中，我们报告了超短肽类模拟物的设计、合成和体外抗菌活性。
• Unprecedented 1,1′-Carbonyldiimidazole-Mediated Amidation of ­Unprotected α-Amino Acids in Water
  作者：Rahul Jain、Rohit Sharma

  DOI：10.1055/s-2007-967965

  日期：——

  The first amidation reaction of unprotected α-amino acids in water under neutral conditions with various aliphatic, aromatic and heteroaromatic amines in the presence of coupling reagent 1,1 '-carbonyldiimidazole at ambient temperature is described.

  描述了在中性条件下，在偶联试剂 1,1'-羰基二咪唑的存在下，在中性条件下，未保护的 α-氨基酸在水中与各种脂肪族、芳香族和杂芳香族胺在环境温度下的第一次酰胺化反应。
• Discovery of Trp-His and His-Arg Analogues as New Structural Classes of Short Antimicrobial Peptides
  作者：Rohit K. Sharma、Ravi P. Reddy、Werner Tegge、Rahul Jain

  DOI：10.1021/jm900622d

  日期：2009.12.10

  Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. In search of short antimicrobial peptides, which represent a possible alternative for lead structures to fight antibiotic resistant microbial infections, a series of synthetic peptide analogues based oil Trp-His and His-Arg structural frameworks have been prepared and found to be active against several Gram-negative and Gram-positive bacterial strains as well as against a fungal strain with MIC values of the most potent Structures in the range of 5-20 mu g/mL ((IC50 in the range of 1-5 mu g/mL). The synthesized peptides showed no cytotoxic effect in an MTT assay up to the highest test concentration of 200 mu g/mL. A combination of small size, presence of unnatural amino acids, high antimicrobial activity, and absence of cytotoxicity reveals the synthesized Trp-His and His-Arg analogues as promising candidates for novel antimicrobial therapeutics.
• Weitzel; Renner; Guglielmi, Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1971, vol. 352, # 12, p. 1617 - 1630
  作者：Weitzel、Renner、Guglielmi

  DOI：——

  日期：——