acetylphenylalanylarginylserinamide | 67055-79-2

• 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: acetylphenylalanylarginylserinamide
• 英文别名: Ac-Phe-Arg-Ser-NH2；(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-N-[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]-5-(diaminomethylideneamino)pentanamide
• CAS: 67055-79-2
• 化学式: C₂₀H₃₁N₇O₅
• 分子量: 449.51
• InChiKey: HVLFXNHKZMVSAK-JYJNAYRXSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  215
• 氢给体数：
  7
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  BOC-L-苯丙氨酸 、 N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 、 N-BOC-O-苄基-L-丝氨酸 、 乙酸酐 生成 acetylphenylalanylarginylserinamide
  参考文献：
  名称：

  Mapping the binding site of tissue kallikrein: preparation and testing of all possible substrate analog inhibitors homologous with the sequence of kininogen between Ser386 and Gln392

  摘要：

  Programs aimed at converting peptide inhibitors of proteolytic enzymes into more traditional drug structures require an understanding of the role played by the individual amino acid residues in the inhibitor. To this end, all possible substrate analogues occurring within the sequence Ser-Pro-Phe-Arg-Ser-Val-Gln392 from bovine kininogen were synthesized and tested as inhibitors of tissue kallikrein (EC 3.4.21.35, beta-PPK). Of the 21 sequences which can be formed from the heptapeptide, 11 have inhibitory constants which could be measured in the chromogenic assay employed in these studies. No dipeptide and only one tripeptide, Ac-Phe-Arg-Ser-NH2 (K(i) = 718-mu-M), measurably inhibits the enzyme. All longer peptides inhibit beta-PPK. The heptapeptide Ac-Ser-Pro-Phe-Arg-Ser-Val-Gln-NH2 is the most effective inhibitor in this series (K(i) = 101-mu-M). Each amino acid residue in the sequence appears to alter binding in a relatively independent manner. The N-terminal seryl residue (P4) and the prolyl residue (P3) slightly improve the K(i) of the various inhibitors. The phenylalanyl residue at P2 appears to have a more pronounced effect on K(i). The arginyl residue at P1 and the seryl residue at P1' appear to be the most important residues in the inhibitory sequence. They contribute approximately one-third and one-fourth of the binding energy to the interaction between the substrate analogues and beta-PPK, respectively. The valyl residue at P2', and the C-terminal glutaminyl residue improve K(i) of each of the peptides tested. Almost 80% of the binding energy of the substrate analogue inhibitors comes from the core sequence Phe-Arg-Ser which occurs between P2 and P1'. Molecular models developed from the Chen-Bode coordinates of the aprotinin-beta-PPK complex have been used to interpret the results of these studies.

  DOI：

  10.1021/jm00095a002

文献信息

• Mapping the binding site of tissue kallikrein: preparation and testing of all possible substrate analog inhibitors homologous with the sequence of kininogen between Ser386 and Gln392
  作者：Milind S. Deshpande、James Burton

  DOI：10.1021/jm00095a002

  日期：1992.8

  Programs aimed at converting peptide inhibitors of proteolytic enzymes into more traditional drug structures require an understanding of the role played by the individual amino acid residues in the inhibitor. To this end, all possible substrate analogues occurring within the sequence Ser-Pro-Phe-Arg-Ser-Val-Gln392 from bovine kininogen were synthesized and tested as inhibitors of tissue kallikrein (EC 3.4.21.35, beta-PPK). Of the 21 sequences which can be formed from the heptapeptide, 11 have inhibitory constants which could be measured in the chromogenic assay employed in these studies. No dipeptide and only one tripeptide, Ac-Phe-Arg-Ser-NH2 (K(i) = 718-mu-M), measurably inhibits the enzyme. All longer peptides inhibit beta-PPK. The heptapeptide Ac-Ser-Pro-Phe-Arg-Ser-Val-Gln-NH2 is the most effective inhibitor in this series (K(i) = 101-mu-M). Each amino acid residue in the sequence appears to alter binding in a relatively independent manner. The N-terminal seryl residue (P4) and the prolyl residue (P3) slightly improve the K(i) of the various inhibitors. The phenylalanyl residue at P2 appears to have a more pronounced effect on K(i). The arginyl residue at P1 and the seryl residue at P1' appear to be the most important residues in the inhibitory sequence. They contribute approximately one-third and one-fourth of the binding energy to the interaction between the substrate analogues and beta-PPK, respectively. The valyl residue at P2', and the C-terminal glutaminyl residue improve K(i) of each of the peptides tested. Almost 80% of the binding energy of the substrate analogue inhibitors comes from the core sequence Phe-Arg-Ser which occurs between P2 and P1'. Molecular models developed from the Chen-Bode coordinates of the aprotinin-beta-PPK complex have been used to interpret the results of these studies.