Discovery and design of novel vasopressin hypotensive peptide agonists

作     者：Manning, M Stoev, S Cheng, LL Wo, NC Chan, WY 

作者机构：Med Coll Ohio Dept Biochem & Mol Biol Toledo OH 43614 USA Cornell Univ Coll Med Dept Pharmacol New York NY 10021 USA 

出 版 物：《JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH》 (受体与信号转导杂志)

年 卷 期：1999年第19卷第1-4期

页      面：631-644页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：NIGMS NIH HHS [GM-25280] Funding Source: Medline 

主　　题：亲和力标记物 氨基酸序列 抗高血压药/化学合成 抗高血压药/化学 抗高血压药/药理学 精氨酸加压素/类似物和衍生物 精氨酸加压素/化学 精氨酸加压素/药理学 药物设计 受体 催产素/拮抗剂和抑制剂 受体 血管升压素/拮抗剂和抑制剂 构效关系 血管升压素类/激动剂 动物 女(雌)性 大鼠 

摘      要：This presentation will trace the serendipitous discovery of novel vasopressin (VP) hypotensive agonists d(CH(2))(5)[D-Tyr(Et)(2),X(3)]VAVP (where X = Arg, Lys). These peptides were uncovered as part of an ongoing program aimed at the design of potent and selective VP antidiuretic (V(2) receptor) antagonists. We will also present highlights of our subsequent preliminary studies seeking (i) to design high affinity radioiodinatable ligands for the localization and characterization of the putative VP vasodilatory (V(1c) ?) receptor;(ii) to identify the structural features of selective and non-selective cyclic and linear VP and oxytocin (OT) antagonists of the V(2) receptor, the vascular (V(1a)) receptor and of the uterine (OT) receptor required for hypotensive agonism and;(iii) to enhance hypotensive potency. These novel VP hypotensive agonists could serve as valuable research tools in studies on the roles of VP in blood pressure regulation and may also lead to the development of a new class of therapeutically useful antihypertensives.