Design of a highly potent anti-hypertensive peptide based on ovokinin(2-7)

Ovokinin(2-7) (RADHPF), an orally active anti-hypertensive 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 [Pro sup(2), Phe sup(3)]-ovokinin(2-7), which was previously reported to have 33-fold stronger activity than ovokinin(2-7). The anti-hypertensive activity of [Pro sup(2), Phe sup(3)]-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 ob-tained, showed significant anti-hypertensive activities at a dose of 0.1 mg/kg after oral administration in sponta-neously hypertensive rats (SHRs). Thus, RPLKPW showed 100-fold more potent anti-hypertensive activity than ovokinin(2-7). 0007 kara