Design of a genetically modified soybean protein preventing hypertension based on an anti-hypertensive peptide derived from ovalbumin.
Food proteins can be a source of various bioactive peptides including such possessing anti-hypertensive activity. While most orally active anti-hypertensive peptides derived from food proteins inhibit the angiotensin I-converting enzyme (ACE), ovokinin (2-7) (RADHPF), a peptide isolated from a chymotryptic digest of ovalbumin, has been shown to induce nitric oxide-dependent vasorelaxation in an isolated mesenteric artery as well as anti-hypertensive effect after oral administration in spontaneously hypertensive rats (SHRs). Rational amino acid replacement lead to the ovokinin (2-7) analog, RPLKPW, which had the highest anti-hypertensive activity among the tested peptides. Furthermore, oral administration (0.1 mg/kg) of the peptide lowered the blood pressure of SHR but not of normotensive Wistar-Kyoto (WKY) rats. In order to develop a novel use of this potent anti-hypertensive peptide for prevention of hypertension, RPLKPW has been genetically introduced into the homologous sequences in soybean beta-conglycinin alpha' subunit by site-directed mutagenesis. The recombinant RPLKPW-incorporated alpha' subunit expressed in E. coil has been shown to exert anti-hypertensive activity after oral administration in SHR. Thus, RPLKPW-incorporated alpha' subunit is the first example of a genetically modified food protein possessing physiological activity based on a bioactive peptide.
Division of Food Bioscience and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Nobuyuki
N
Matoba
Yuko
Y
Yamada
Masaaki
M
Yoshikawa
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015195:Drug Design; D004527:Egg Proteins / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D016297:Mutagenesis, Site-Directed; D009569:Nitric Oxide / Q000378:metabolism; D010047:Ovalbumin / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D030262:Soybean Proteins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D004527:Egg Proteins; D010446:Peptide Fragments; D030262:Soybean Proteins; C096585:ovokinin; D009569:Nitric Oxide; D010047:Ovalbumin; D007703:Peptidyl-Dipeptidase A