Asp-Thr-His-NH2 | 1315573-04-6

• 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: Asp-Thr-His-NH2
• CAS: 1315573-04-6
• 化学式: C₁₄H₂₂N₆O₆
• 分子量: 370.365
• InChiKey: PNYAJNKHUGFHSB-PBCZWWQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.41
• 重原子数：
  26.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  213.52
• 氢给体数：
  7.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  N-Boc-O-苄基-L-苏氨酸 、 Boc-L-天冬氨酸-4-环己酯 、 N-Boc-N'-苄氧甲基-L-组氨酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 Asp-Thr-His-NH2
  参考文献：
  名称：

  Interactions of di-imine copper(II) complexes with albumin: competitive equilibria, promoted oxidative damage and DFT studies

  摘要：

  Interactions of some diimine copper(II) complexes with bovine serum albumin (BSA) were investigated by spectroscopic techniques in order to compare the stability of the complexes and their capability of causing oxidative damage to the protein. The tri- and tetradentate imine ligands employed in this work contain pyridine, pyrazine or imidazole moieties, which are ubiquitous in biological systems. The relative thermodynamic stabilities of the copper(II) complexes were estimated by circular dichroism (CD) using BSA as the competitive ligand. The apparent stability constants determined for the complexes are very similar to one another and to that of the Cu(BSA) complex itself, for which log K-Cu(BSA) = 12.9 has already been described in the literature, indicating that the complexes are quite stable under physiological conditions. Two different copper binding sites were evidenced on BSA by spectroscopic measurements (CD, UV-Vis and EPR), depending on the ligand and on the [CuL]:[protein] stoichiometric ratio. Metal binding to any of the sites gives rise to significant protein oxidative damage, especially in the presence of hydrogen peroxide, indicating an oxidative process based on reactive oxygen species (ROS). A small amidated peptide, Asp-Thr-His-NH2, corresponding to the N-terminal region of BSA was synthesized, and its interaction with all the diimine-copper(II) complexes was also investigated in order to clarify the copper imine complex-albumin interactions. Electronic structure calculations at the density functional theory (DFT) level were made to compare the copper-ligand binding energies for each complex with that of the metal coordinated at the N-terminal site of the protein.

  DOI：

  10.1590/s0103-50532010000700018

文献信息

• Improved Bioactivity of Antimicrobial Peptides by Addition of Amino-Terminal Copper and Nickel (ATCUN) Binding Motifs
  作者：M. Daben Libardo、Jorge L. Cervantes、Juan C. Salazar、Alfredo M. Angeles-Boza

  DOI：10.1002/cmdc.201402033

  日期：2014.5.6

  Antimicrobial peptides (AMPs) are promising candidates to help circumvent antibiotic resistance, which is an increasing clinical problem. Amino‐terminal copper and nickel (ATCUN) binding motifs are known to actively form reactive oxygen species (ROS) upon metal binding. The combination of these two peptidic constructs could lead to a novel class of dual‐acting antimicrobial agents. To test this hypothesis

  抗菌肽 (AMP) 是帮助规避抗生素耐药性的有希望的候选者，这是一个日益严重的临床问题。已知氨基末端铜和镍 (ATCUN) 结合基序在金属结合时会主动形成活性氧 (ROS)。这两种肽结构的组合可以产生一类新型的双作用抗菌剂。为了验证这一假设，筛选了一组 ATCUN 结合基序的诱导 ROS 形成能力，然后使用最有效的基序来修饰具有不同作用模式的 AMP。含 ATCUN 结合基序的 anoplin (GLLKRIKTLL-NH 2 )、促凋亡肽 (PAP; KLAKLAKKLAKLAK-NH 2 ) 和sh -buforin (RAGLQFPVGRVHRLLRK-NH 2) 的衍生物) 被合成并发现对一组临床相关细菌比亲本 AMP 更具活性。ATCUN-anoplin 肽较低的最小抑制浓度 (MIC) 值归因于较高的成孔活性以及它们引起 ROS 诱导的膜损伤的能力。将 ATCUN 基序添加到 PAP