Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-NH2 | 111113-26-9

• 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-Ftr-Pro-Phe-His-Phe-Phe-Val-NH2
• 英文别名: (2S)-1-[(2S)-2-acetamido-3-(1-formylindol-3-yl)propanoyl]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pyrrolidine-2-carboxamide
• CAS: 111113-26-9
• 化学式: C₅₇H₆₅N₁₁O₉
• 分子量: 1048.21
• InChiKey: RBGWJHVZGMCNNR-BODWXVGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  77
• 可旋转键数：
  24
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  289
• 氢给体数：
  8
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  BOC-L-脯氨酸 、 BOC-L-苯丙氨酸 、 Nalpha-叔丁氧羰基-N-对甲苯磺酰基-L-组氨酸二环己胺盐 、 alkaline earth salt of/the/ methylsulfuric acid 生成 Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-NH2
  参考文献：
  名称：

  Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu.psi.[CH(OH)CH2]Val or Leu.psi.[CH2NH]Val substitutions

  摘要：

  A structure-conformation-activity investigation of several angiotensinogen (ANG) based inhibitors of human renin modified by either Phe-Phe, Sta, Leu psi[CH2NH]Val, or Leu psi[CH(OH)CH2]Val at the P1-P1' clevage site and P5 Trp(Nin-For) (Ftr) was performed. Specifically, Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-Ftr-NH2 (1) provided a potent (KI = 2.7 X 10(-8) M) P1-P1' Phe-Phe substituted renin inhibitor to initiate these studies. Substitution of the P1-P1' Phe-Phe in compound 1 by Sta effected a 1,000-fold increase in biological potency for the resultant octapeptide Ac-Ftr-Pro-Phe-His-Sta-Val-Ftr-NH2 (10; KI = 6.7 X 10(-11) M). Kinetic analysis of compound 10 showed it to be a competitive inhibitor of human renin catalyzed proteolysis of human ANG. Chemical modifications of the compounds 1 and 10 were evaluated on the basis of comparative human plasma renin inhibitory activities (IC50 values) in vitro. Carboxy-terminal truncation studies on compound 10 showed that the P2' Val and P3' Ftr residues could both be eliminated without significant loss (ca. 10-fold) in renin inhibitory activity as exemplified by the pentapeptide Ac-Ftr-Pro-Phe-His-Sta-NH2 (12; IC50 = 3.8 X 10(-9) M). In addition, the corresponding P1-P1' Leu psi[CH(OH)CH2]Val and Leu psi[CH2NH]Val derivatives of compound 12 were potent renin inhibitors: Ac-Ftr-Pro-Phe-His-Leu psi[CH(OH)CH2]Val-NH2 (13; IC50 = 3.1 X 10(-10) M) and Ac-Ftr-Pro-Phe-His-Leu psi[CH2NH]Val-NH2 (14; IC50 = 2.1 X 10(-8) M). The structure-conformation-activity properties of the N-terminal Ftr substitution of these human renin inhibitors was examined by (1) comparative analysis of several analogues of 1 and Ac-Ftr-Pro-Phe-His-Sta-Ile-NH2 (17; IC50 = 1.0 X 10(-10) M) having P5 site modifications by Trp, His, D-Ftr, and D-His, (2) deletion of the N-terminal Ftr residue from compounds 12 and 17, to provide Ac-Pro-Phe-His-Sta-Ile-NH2 (16; IC50 = 3.1 X 10(-8) M) and Ac-Pro-Phe-His-Sta-NH2 (15; IC50 = 5.6 X 10(-6) M), and (3) computer modeling and dynamics studies of compounds 1 and 17 bound to CKH-RENIN, a simulated human renin model, which were focused on identifying potential intermolecular interactions of their common P5-P2 sequence, Ac-Ftr-Pro-Phe-His, at the enzyme active site.(ABSTRACT TRUNCATED AT 400 WORDS)

  DOI：

  10.1021/jm00396a006

文献信息

• Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu.psi.[CH(OH)CH2]Val or Leu.psi.[CH2NH]Val substitutions
  作者：Tomi K. Sawyer、Donald T. Pals、Boryeu Mao、Douglas J. Staples、Anne E. DeVaux、Linda L. Maggiora、Joseph A. Affholter、Warren Kati、David Duchamp

  DOI：10.1021/jm00396a006

  日期：1988.1

  A structure-conformation-activity investigation of several angiotensinogen (ANG) based inhibitors of human renin modified by either Phe-Phe, Sta, Leu psi[CH2NH]Val, or Leu psi[CH(OH)CH2]Val at the P1-P1' clevage site and P5 Trp(Nin-For) (Ftr) was performed. Specifically, Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-Ftr-NH2 (1) provided a potent (KI = 2.7 X 10(-8) M) P1-P1' Phe-Phe substituted renin inhibitor to initiate these studies. Substitution of the P1-P1' Phe-Phe in compound 1 by Sta effected a 1,000-fold increase in biological potency for the resultant octapeptide Ac-Ftr-Pro-Phe-His-Sta-Val-Ftr-NH2 (10; KI = 6.7 X 10(-11) M). Kinetic analysis of compound 10 showed it to be a competitive inhibitor of human renin catalyzed proteolysis of human ANG. Chemical modifications of the compounds 1 and 10 were evaluated on the basis of comparative human plasma renin inhibitory activities (IC50 values) in vitro. Carboxy-terminal truncation studies on compound 10 showed that the P2' Val and P3' Ftr residues could both be eliminated without significant loss (ca. 10-fold) in renin inhibitory activity as exemplified by the pentapeptide Ac-Ftr-Pro-Phe-His-Sta-NH2 (12; IC50 = 3.8 X 10(-9) M). In addition, the corresponding P1-P1' Leu psi[CH(OH)CH2]Val and Leu psi[CH2NH]Val derivatives of compound 12 were potent renin inhibitors: Ac-Ftr-Pro-Phe-His-Leu psi[CH(OH)CH2]Val-NH2 (13; IC50 = 3.1 X 10(-10) M) and Ac-Ftr-Pro-Phe-His-Leu psi[CH2NH]Val-NH2 (14; IC50 = 2.1 X 10(-8) M). The structure-conformation-activity properties of the N-terminal Ftr substitution of these human renin inhibitors was examined by (1) comparative analysis of several analogues of 1 and Ac-Ftr-Pro-Phe-His-Sta-Ile-NH2 (17; IC50 = 1.0 X 10(-10) M) having P5 site modifications by Trp, His, D-Ftr, and D-His, (2) deletion of the N-terminal Ftr residue from compounds 12 and 17, to provide Ac-Pro-Phe-His-Sta-Ile-NH2 (16; IC50 = 3.1 X 10(-8) M) and Ac-Pro-Phe-His-Sta-NH2 (15; IC50 = 5.6 X 10(-6) M), and (3) computer modeling and dynamics studies of compounds 1 and 17 bound to CKH-RENIN, a simulated human renin model, which were focused on identifying potential intermolecular interactions of their common P5-P2 sequence, Ac-Ftr-Pro-Phe-His, at the enzyme active site.(ABSTRACT TRUNCATED AT 400 WORDS)