Ac-L-Met-Gly-L-His-GlyNH2 | 1197421-58-1

• 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: Ac-L-Met-Gly-L-His-GlyNH2
• 英文别名: Ac-Met-Gly-His-Gly-NH2；(2S)-2-acetamido-N-[2-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-4-methylsulfanylbutanamide
• CAS: 1197421-58-1
• 化学式: C₁₇H₂₇N₇O₅S
• 分子量: 441.511
• InChiKey: XFNYISKCBPIHGU-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  214
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ac-L-Met-Gly-L-His-GlyNH2 、 {[Pt(ethylenediamine)(H₂O)]₂(μ-pyridazine)}⁴⁺ 反应 0.17h， 生成 {[Pt(ethylenediamine)(Ac-(l-methionylglycyl-l-histidylglycineamide)NH₂-S)](μ-pyridazine)[Pt(ethylenediamine)(H₂O)]}⁴⁺
  参考文献：
  名称：

  Disparate behavior of pyrazine and pyridazine platinum(II) dimers in the hydrolysis of histidine- and methionine-containing peptides and unique crystal structure of {[Pt(en)Cl]2(μ-pydz)}Cl2 with a pair of NH⋯Cl−⋯HN hydrogen bonds supporting the pyridazine bridge

  摘要：

  Treatment of [Pt(en)Cl-2] complex with pyridazine lead to the formation of new diplatinum(II) coordination compound {[Pt(en)CIl(2)(mu-pydz))Cl-2, which was characterized by NMR spectroscopy and single-crystal X-ray diffraction. X-ray analysis revealed that the needed support for the pyridazine bridge formation, which in other metal complexes has been mostly provided by additional bridging units coordinated to metal centers, might come from supramolecular interactions such as intermolecular hydrogen bonds. This complex was converted into the corresponding aqua complex, {[Pt(en)(H2O)](2)(mu-pydz))(4+), and 1H NMR spectroscopy was applied for comparison of its catalytic activity with that of the analogous pyrazine-bridged {[Pt(en)(H2O)](2)(P-Pz))(4) complex in the hydrolysis of the N-acetylated L-histidylglycine (Ac-L-His-Gly) and L-methionyl-glycyl-L-histidyl-glycineamide (Ac-L-Met-Gly-L-His-GlyNH(2)). All reactions were performed in the pH range 2.0-2.5 and at 37 degrees C. It was found that although dimerization, in general, improves significantly the hydrolytic potency of Pt(II) complexes, the pyridazine Pt(II) dimer is significantly less active than its pyrazine Pt(II) analog, which is probably due to an increased steric effect exerted in the former complex by the ortho-position of the two nitrogen atoms. Consequently, {[Pt(en)(H2O)](2)(mu-pydz))(4+) only binds to the methionine sulfur atom of the Ac-L-Met-Gly-L-His-GlyNFI(2) peptide and promotes cleavage of amide bond that involves the carboxylic group of methionine. In contrast, the analogous pyrazine Pt(II) dimer reacts with both methionine and histidine residues of this tetrapeptide, promoting cleavage of amide bonds involving carboxylic groups of both of these anchoring amino acids. Considering these results it can be assumed that in the polypeptide containing both methionine and histidine residues the regioselective cleavage of the amide bond involving only the carboxylic group of methionine can be achieved successfully by using the presently investigated pyridazine-bridged Pt(II) complex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2013.09.008

文献信息

• 1H NMR study of the reactions between carboplatin analogues [Pt(en)(Me-mal-O,O′)] and [Pt(en)(Me2-mal-O,O′)] and various methionine- and histidine-containing peptides under physiologically relevant conditions
  作者：Snežana Rajković、Darko P. Ašanin、Marija D. Živković、Miloš I. Djuran

  DOI：10.1016/j.ica.2012.11.004

  日期：2013.1

  H-1 NMR spectroscopy was applied to the study the reactions of [Pt(en)(Me-mal-O,O')] and [Pt(en)(Me-2-mal-O,O')] complexes (en is ethylenediamine, Me-mal and Me-2-mal are bidentate coordinated anions of 2-methylmalonic and 2,2-dimethylmalonic acids, respectively) with N-acetylated Ac-L-Met-Gly and Ac-L-Met-L-His-type peptides (Ac-L-Met-L-His, Ac-L-Met-Gly-L-His-GlyNH(2) and Ac-L-Met-Gly-Gly-L-His-Gly). The use of Me-mal and Me2-mal Pt(II) complexes in the above reactions allows convenient monitoring of their biscarboxylate group via methyl peaks by H-1 NMR measurements. All reactions were realized at 37 degrees C with equimolar amounts of the Pt(II) complex and the dipeptide at pH 7.40 in 50 mM phosphate buffer in D2O. In all these reactions the ring-opened Me-mal and Me-2-mal Pt(II) adducts as an intermediate products were detected in solution for more than 48 h. We found that during this time in the reaction with Ac-L-Met-Gly these monodentate bound malonate ligands have been replaced by water molecule leading to the formation of the corresponding aqua Pt(II)-peptide complex which further promotes the regioselective cleavage of the peptide. However, in the reaction with Ac-L-Met-L-His-type peptides a selective intramolecular replacement of these malonate anions by the N3 imidazole nitrogen atom from histidine residue was occurred. This replacement reaction leads to the formation of the S, N3-macrochelate Pt(II)-peptide complex which was shown as very stable and hydrolytically inactive for more than two weeks. (c) 2012 Elsevier B.V. All rights reserved.