从血管紧张素 II 到环肽和血管紧张素受体阻滞剂 (ARB):ARB 在 COVID-19 治疗中的观点。

From Angiotensin II to Cyclic Peptides and Angiotensin Receptor Blockers (ARBs): Perspectives of ARBs in COVID-19 Therapy.

机构信息

Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia.

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

出版信息

Molecules. 2021 Jan 25;26(3):618. doi: 10.3390/molecules26030618.

Abstract

The octapeptide hormone angiotensin II is one of the most studied peptides with the aim of designing and synthesizing non-peptide mimetics for oral administration. To achieve this, cyclizations at different positions within the peptide molecule has been a useful strategy to define the active conformation. These studies on angiotensin II led to the discovery of Sarmesin, a type II angiotensin II antagonist, and the breakthrough non-peptide mimetic Losartan, the first in a series of sartans marketed as a new generation of anti-hypertensive drugs in the 1990s. Angiotensin II receptor blockers (ARBS) and angiotensin I converting enzyme inhibitors (ACEI) were recently reported to protect hypertensive patients infected with SARS-CoV-2. The renin-angiotensin system (RAS) inhibitors reduce excess angiotensin II and increase antagonist heptapeptides alamandine and aspamandine which counterbalance angiotensin II and maintain homeostasis and vasodilation.

摘要

八肽激素血管紧张素 II 是研究最多的肽类之一,其目的是设计和合成可口服的非肽模拟物。为此,在肽分子的不同位置进行环化已成为定义活性构象的有用策略。这些对血管紧张素 II 的研究导致了 Sarme 素的发现,Sarme 素是一种 II 型血管紧张素 II 拮抗剂,以及突破性的非肽模拟物 Losartan,它是 20 世纪 90 年代作为新一代抗高血压药物上市的一系列沙坦类药物中的第一个。最近有报道称,血管紧张素 II 受体阻滞剂 (ARBS) 和血管紧张素转换酶抑制剂 (ACEI) 可保护感染 SARS-CoV-2 的高血压患者。肾素-血管紧张素系统 (RAS) 抑制剂可减少过量的血管紧张素 II 并增加拮抗剂七肽 alamandine 和 aspamandine,它们可对抗血管紧张素 II 并维持体内平衡和血管舒张。

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