C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 14/705 (2006.01) A61K 38/04 (2006.01) A61K 38/17 (2006.01) A61K 39/395 (2006.01) C07K 5/08 (2006.01) C07K 5/10 (2006.01) C07K 5/103 (2006.01) C07K 7/06 (2006.01) C07K 7/14 (2006.01) G01N 33/566 (2006.01) G01N 33/577 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2139105
A unique and novel angioten- sin AT4 receptor and AIV ligand sys- tem for binding a small N-terminal hexapeptide fragment of Angiotensin II (referred to as AIV, with amino ac- id sequence Val1-Tyr2-Ile3-His4-Pro5-Phe6) is disclosed. AIV ligand binds satu- rably, reversibly, specifically, and with high affinity to membrane AT4 receptors in a variety of tissues, in- cluding heart, lung, kidney, aorta, brain, liver, and uterus, from many animal species. The AT4 receptor is pharmacologically distinct from classic angiotensin receptors (AT1 or AT2). The system employs AIV or C-terminally truncated or ex- tended AIV-like peptides (e.g. VY- IHPFX) as the signaling agent, and the AT4 plasma membrane receptor as the detection mechanism. The an- giotensin AT4 receptor and receptor fragments (including the receptor binding site domain) are capable of binding a VYIHPF angiotensin AIV N-terminal peptide but not an angiotensin AII or AIII N-terminal peptide, i.e., DRVYIHPF or RVYIHPF, respectively. Also disclosed are processes for isolating angiotensin AT4 receptor and AIV angiotensinase, identifying angiotensin AIV agonists and antagonists, and constructing diagnostic assays to specifically measure AIV and AI-specific angiotensinase in biological fluids.
Harding Joseph W.
Wright John W.
Smart & Biggar
Washington State University Research Foundation
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