Design of a highly potent anti-hypertensive peptide based on ovokinin(2-7).
Ovokinin(2-7) (RADHPF), an orally active antihypertensive peptide derived from ovalbumin, lowers blood pressure in SHRs at a dose of 10 mg/kg. Attempts were made to potentiate its anti-hypertensive activity by replacing the amino acid residues in [Pro2, Phe3]-ovokinin(2-7), which was previously reported to have 33-fold stronger activity than ovokinin(2-7). The anti-hypertensive activity of [Pro2, Phe3]-ovokinin(2-7) was improved by replacement of the C-terminal Phe residue with Trp. Then, the best amino acid residues at other positions for the anti-hypertensive effect were selected. RPLKPW, the most potent derivative obtained, showed significant anti-hypertensive activities at a dose of 0.1 mg/kg after oral administration in spontaneously hypertensive rats (SHRs). Thus, RPLKPW showed 100-fold more potent anti-hypertensive activity than ovokinin(2-7).
Yamada
Yuko
Y
Division of Food Bioscience and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Japan.
Matoba
Nobuyuki
N
Usui
Hachiro
H
Onishi
Kunihiko
K
Yoshikawa
Masaaki
M
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007275:Injections, Intravenous; D008297:Male; D010047:Ovalbumin / Q000737:chemistry*; D010194:Pancreatin / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000959:Antihypertensive Agents; D010446:Peptide Fragments; C119914:ovalbumin (359-364); D010194:Pancreatin; D010047:Ovalbumin