亮氨酸-缬氨酸-苯丙氨酸-甲氧基（Leu-Val-Phe-OCH3）的N-（α-羟基烷酰基）衍生物作为肾素抑制剂

N-(alpha-Hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 as inhibitors of renin.

作者信息

Johnson R L

出版信息

J Med Chem. 1980 Jun;23(6):666-9. doi: 10.1021/jm00180a017.

DOI:10.1021/jm00180a017

Abstract

The following N-(alpha-hydroxylakanoyl) derivatives of Leu-Val-Phe-OCH3 were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-alpha-hydroxyphenylacetyl-Leu-Val-Phe-OCH3. Analysis of the compounds through the use of Dixion plots showed all of the compounds to be competitive inhibitors of renin. All but D-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were found to be more active than the known tetrapeptide inhibitor Leu-Leu-Val-Phe-OCH3 (1). The two most active compounds of the series were L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (Ki = 0.23 mM) and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (Ki = 0.3 mM).

摘要

合成了以下亮氨酸 - 缬氨酸 - 苯丙氨酸 - 甲氧基（Leu-Val-Phe-OCH3）的N -（α - 羟基链烷酰基）衍生物，并测试了它们抑制人羊膜肾素的能力：D - 和L - α - 羟基异己酰基 - Leu-Val-Phe-OCH3、D - 和L - α - 羟基异戊酰基 - Leu-Val-Phe-OCH3、L - 2 - 羟基 - 3 - 苯基丙酰基 - Leu-Val-Phe-OCH3以及D - 和L - α - 羟基苯乙酰基 - Leu-Val-Phe-OCH3。通过使用迪克森图对这些化合物进行分析，结果表明所有化合物都是肾素的竞争性抑制剂。除D - α - 羟基异戊酰基 - Leu-Val-Phe-OCH3外，所有化合物均比已知的四肽抑制剂亮氨酸 - 亮氨酸 - 缬氨酸 - 苯丙氨酸 - 甲氧基（Leu-Leu-Val-Phe-OCH3）（1）更具活性。该系列中活性最高的两种化合物是L - α - 羟基异己酰基 - Leu-Val-Phe-OCH3（Ki = 0.23 mM）和L - α - 羟基异戊酰基 - Leu-Val-Phe-OCH3（Ki = 0.3 mM）。

相似文献

1

N-(alpha-Hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 as inhibitors of renin.亮氨酸-缬氨酸-苯丙氨酸-甲氧基（Leu-Val-Phe-OCH3）的N-（α-羟基烷酰基）衍生物作为肾素抑制剂

J Med Chem. 1980 Jun;23(6):666-9. doi: 10.1021/jm00180a017.

2

Renin inhibitors. Substitution of the leucyl residues of Leu-Leu-Val-Phe-OCH3 with 3-amino-2-hydroxy-5-methylhexanoic acid.肾素抑制剂。用3-氨基-2-羟基-5-甲基己酸取代Leu-Leu-Val-Phe-OCH3的亮氨酰残基。

J Med Chem. 1982 May;25(5):605-10. doi: 10.1021/jm00347a024.

3

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.具有N端Nin-For-Trp（Ftr）的强效肾素抑制肽的设计、构效关系及分子模拟研究：经P1-P1'苯丙氨酸-苯丙氨酸、斯塔汀、亮氨酸ψ[CH(OH)CH2]缬氨酸或亮氨酸ψ[CH2NH]缬氨酸取代修饰的血管紧张素原类似物

J Med Chem. 1988 Jan;31(1):18-30. doi: 10.1021/jm00396a006.

4

Synthesis of six analogues and their two fragments related to L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OMe as renin inhibitor.

Biochem Biophys Res Commun. 1981 May 15;100(1):177-83. doi: 10.1016/s0006-291x(81)80079-4.

5

Inhibition of renin by angiotensinogen peptide fragments containing the hydroxy amino acid residue 5-amino-3-hydroxy-7-methyloctanoic acid.含羟基氨基酸残基5-氨基-3-羟基-7-甲基辛酸的血管紧张素原肽片段对肾素的抑制作用。

J Med Chem. 1983 Oct;26(10):1457-62. doi: 10.1021/jm00364a019.

6

Inhibition of renin by substrate analogue inhibitors containing the olefinic amino acid 5(S)-amino-7-methyl-3(E)-octenoic acid.含烯属氨基酸5(S)-氨基-7-甲基-3(E)-辛烯酸的底物类似物抑制剂对肾素的抑制作用

J Med Chem. 1984 Oct;27(10):1351-4. doi: 10.1021/jm00376a023.

7

Active site directed inactivators of mouse submaxillary renin.小鼠颌下腺肾素的活性位点导向失活剂。

Biochemistry. 1975 Jul 15;14(14):3188-94. doi: 10.1021/bi00685a024.

8

Competitive inhibitors of renin. Inhibitors effective at physiological pH.

Biochemistry. 1975 Aug 26;14(17):3892-8. doi: 10.1021/bi00688a024.

9

Novel inhibitors of human renin. Cyclic peptides based on the tetrapeptide sequence Glu-D-Phe-Lys-D-Trp.新型人肾素抑制剂。基于四肽序列Glu-D-Phe-Lys-D-Trp的环肽。

J Med Chem. 1990 Sep;33(9):2552-60. doi: 10.1021/jm00171a033.

10

Kinetics of the inhibition of human renin by an inhibitor containing a hydroxyethylene dipeptide isostere.

Biochemistry. 1987 Dec 1;26(24):7621-6. doi: 10.1021/bi00398a014.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

文档翻译

学术文献翻译模型，支持多种主流文档格式。