含缬氨酸-组氨酸替代物Val ψ[CH(CONH2)NH]His的血管紧张素II类似物的合成及生物活性

Synthesis and biological activity of angiotensin II analogues containing a Val-His replacement, Val psi[CH(CONH2)NH]His.

作者信息

Mohan R, Chou Y L, Bihovsky R, Lumma W C, Erhardt P W, Shaw K J

机构信息

Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.

出版信息

J Med Chem. 1991 Aug;34(8):2402-10. doi: 10.1021/jm00112a014.

DOI:10.1021/jm00112a014

PMID:1875337

Abstract

The dipeptide mimic Val psi[CH(CONH2)NH]His (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralasin derivative (29) as well as tetrapeptide analogue 19. Three C-terminal tetrapeptides (21, 25, and 28) were also prepared. All compounds were tested for their ability to displace 3H-AII from rabbit adrenal gland homogenate and as antagonists of AII and AI on guinea pig ileum. The octapeptide analogue 29 was 700 times less active than the parent peptide 30. All the C-terminal fragments 19, 21, 25, and 28 have no measurable AII antagonist activity. Of the four tetrapeptide fragments, only 21 showed any appreciable binding activity.

摘要

将二肽模拟物缬氨酸ψ[CH(CONH2)NH]组氨酸(4)引入血管紧张素II(AII)类似物中，以提供一种八肽沙拉新衍生物(29)以及四肽类似物19。还制备了三种C末端四肽(21、25和28)。测试了所有化合物从兔肾上腺匀浆中置换3H-AII的能力，以及它们作为AII和AI对豚鼠回肠的拮抗剂的能力。八肽类似物29的活性比母体肽30低700倍。所有C末端片段19、21、25和28均无可测量的AII拮抗剂活性。在四个四肽片段中，只有21表现出任何明显的结合活性。