• J. Recept. Signal Transduct. Res. · Jan 1999

    Discovery and design of novel vasopressin hypotensive peptide agonists.

    • M Manning, S Stoev, L L Cheng, N C Wo, and W Y Chan.
    • Department of Biochemistry & Molecular Biology, Medical College of Ohio, Toledo 43614, USA.
    • J. Recept. Signal Transduct. Res. 1999 Jan 1; 19 (1-4): 631-44.

    AbstractThis presentation will trace the serendipitous discovery of novel vasopressin (VP) hypotensive agonists d(CH2)5[D-Tyr(Et)2,X3]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 (V2 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 (V1c?) receptor; (ii) to identify the structural features of selective and non-selective cyclic and linear VP and oxytocin (OT) antagonists of the V2 receptor, the vascular (V1a) 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.

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