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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 Y., et al. Biosci
Biotechnol Biochem 2002 Jun;66(6):1213-7
Design and production of genetically modified soybean protein with
anti-hypertensive activity by incorporating potent analogue of ovokinin(2-7)
The potent anti-hypertensive peptide, RPLKPW, has been designed based on
the structure of ovokinin(2-7). The sequence encoding this peptide was
introduced into three homologous sites in the gene for soybean
beta-conglycinin alpha' subunit. The native alpha' subunit as well as the
modified, RPLKPW-containing alpha' subunit were expressed in Escherichia
coli, recovered from the soluble fraction and then purified by ion-exchange
chromatography. The RPLKPW peptide was released from recombinant
RPLKPW-containing alpha' subunit after in vitro digestion by trypsin and
chymotrypsin. Moreover, the undigested RPLKPW-containing alpha' subunit given
orally at a dose of 10 mg/kg exerted an anti-hypertensive effect in
spontaneously hypertensive rats, unlike the native alpha' subunit. These
results provide evidence for the first time that a physiologically active
peptide introduced into a food protein by site-directed mutagenesis could
practically function in vivo even at a low dose. Matoba N., et al. FEBS
Lett 2001 May 18;497(1):50-4
Designing potent derivatives of ovokinin(2-7), an
anti-hypertensive peptide derived from ovalbumin
We obtained a potent anti-hypertensive
peptide, RPFHPF, by replacing the amino acid residues of ovokinin(2-7)
(RADHPF), an orally active anti-hypertensive peptide derived from ovalbumin.
After intravenous administration in anesthetized Wistar rats, the designed
peptide [Pro2, Phe3]-ovokinin(2-7) had a long-lasting hypotensive activity at
a dose of 10 mg/kg, while that of ovokinin(2-7) was only transient even at a
dose of 100 mg/kg. After oral administration in conscious spontaneously
hypertensive rats (SHRs), [Pro2, Phe3]-ovokinin(2-7) significantly lowered
the systolic blood pressure in a dose-dependent manner. It is noteworthy that
the minimum effective dose of [Pro2, Phe3]-ovokinin(2-7) was 0.3 mg/kg, about
one-thirtieth of that of ovokinin(2-7). On the other hand, orally
administered [Pro2, Phe3]-ovokinin(2-7) did not show any significant
hypotensive effect in normotensive Wistar-Kyoto rats (WKYs) even at a dose of
3 mg/kg. Taken together, [Pro2, Phe3]-ovokinin(2-7) proved to be an ideal,
potent anti-hypertensive peptide with little effect on normal blood pressure
when given orally. Matoba N., et al. Biosci Biotechnol Biochem 2001
Mar;65(3):736-9
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