(2s)-2,6-Diacetamido-N-Methyl-Hexanamide | 1244956-32-8

• 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)-2,6-Diacetamido-N-Methyl-Hexanamide
• 英文别名: (2S)-2,6-diacetamido-N-methylhexanamide
• CAS: 1244956-32-8
• 化学式: C₁₁H₂₁N₃O₃
• 分子量: 243.306
• InChiKey: RWBIXQSLRNBRKV-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  87.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Ac-Lys(ε-NH3(+))-NHMe 、 乙酸酐 在 PS-DIEA 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以83%的产率得到(2s)-2,6-Diacetamido-N-Methyl-Hexanamide
  参考文献：
  名称：

  Neutralizing Positive Charges at the Surface of a Protein Lowers Its Rate of Amide Hydrogen Exchange without Altering Its Structure or Increasing Its Thermostability

  摘要：

  This paper combines two techniques-mass spectrometry and protein charge ladders to examine the relationship between the surface charge and hydrophobicity of a representative globular protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-epsilon-NH3+ groups-a type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its secondary or tertiary structure resulted in a linear decrease in the aggregate rate of amide H/D exchange at pD 7.4, 15 degrees C. According to analysis with MS, the acetylation of each additional lysine generated between 1.4 and 0.9 additional hydrogens that are protected from HID exchange during the 2 h exchange experiment at 15 degrees C, pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which became protected upon acetylation were located on the side chain of the acetylated lysine residues (i.e., lys-epsilon-NHCOCH3) but were instead located on amide NHCO moieties in the backbone. The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs of the charge ladder were the least thermostable (as measured by differential scanning calorimetry). This observation that faster rates of exchange are associated with slower rates of denaturation is contrary to the usual assumptions in protein chemistry. The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., [lys-epsilon-NHCO(CH2)(2)CH3](18)) and peracetylated BCA II (e.g., [lys-e-NHCOCH3](18)) suggests that the electrostatic charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These electrostatic effects on the kinetics of H/D exchange could complicate (or aid) the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or to another charged ligand or protein).

  DOI：

  10.1021/ja9067035

文献信息

• [EN] COMPOUNDS AND METHODS USEFUL IN BRACHYTHERAPY<br/>[FR] COMPOSÉS ET MÉTHODES UTILES EN CURIETHÉRAPIE
  申请人：UNIV NORTH CAROLINA STATE

  公开号：WO2019165171A2

  公开（公告）日：2019-08-29

  Compounds and methods are described herein that are useful in brachytherapy. A compound of the present invention may comprise: a cancer cell targeting agent (e.g., transferrin); a protecting group; a cross-linking moiety; and an enzyme (e.g., a protein, ribozyme, abzyme, or abiological catalyst). Compounds and methods of the present invention may be used for localizing a radioactive compound and/or for creating a self-amplifying response.
• Neutralizing Positive Charges at the Surface of a Protein Lowers Its Rate of Amide Hydrogen Exchange without Altering Its Structure or Increasing Its Thermostability
  作者：Bryan F. Shaw、Haribabu Arthanari、Max Narovlyansky、Armando Durazo、Dominique P. Frueh、Michael P. Pollastri、Andrew Lee、Basar Bilgicer、Steven P. Gygi、Gerhard Wagner、George M. Whitesides

  DOI：10.1021/ja9067035

  日期：2010.12.15

  This paper combines two techniques-mass spectrometry and protein charge ladders to examine the relationship between the surface charge and hydrophobicity of a representative globular protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-epsilon-NH3+ groups-a type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its secondary or tertiary structure resulted in a linear decrease in the aggregate rate of amide H/D exchange at pD 7.4, 15 degrees C. According to analysis with MS, the acetylation of each additional lysine generated between 1.4 and 0.9 additional hydrogens that are protected from HID exchange during the 2 h exchange experiment at 15 degrees C, pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which became protected upon acetylation were located on the side chain of the acetylated lysine residues (i.e., lys-epsilon-NHCOCH3) but were instead located on amide NHCO moieties in the backbone. The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs of the charge ladder were the least thermostable (as measured by differential scanning calorimetry). This observation that faster rates of exchange are associated with slower rates of denaturation is contrary to the usual assumptions in protein chemistry. The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., [lys-epsilon-NHCO(CH2)(2)CH3](18)) and peracetylated BCA II (e.g., [lys-e-NHCOCH3](18)) suggests that the electrostatic charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These electrostatic effects on the kinetics of H/D exchange could complicate (or aid) the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or to another charged ligand or protein).