Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion.
Whey protein was digested with one of seven kinds of proteases at 37 degrees C (trypsin, proteinase K, actinase E, thermolysin, or papain) or at 25 degrees C (pepsin or chymotrypsin) for 24 h. The digested samples were assayed for the inhibitory activity of angiotensin-converting enzyme and for changes in the systolic blood pressure caused in spontaneously hypertensive rats after gastric intubation. The strongest depressive effect on the systolic blood pressure (-55 mm Hg) was observed at 6 h after gastric intubation of the whey protein that was digested by proteinase K. Finally, six peptides were chromatographically isolated from the proteinase K digest by a combination of hydrophobic reversed-phase HPLC and gel filtration. The amino acid sequences and their origins were clarified as follows: Val-Tyr-Pro-Phe-Pro-Gly [beta-casein (CN); f 59-64], Gly-Lys-Pro (beta 2-microglobulin; f 18-20), Ile-Pro-Ala (beta-lactoglobulin; f 78-80), Phe-Pro (serum albumin; f 221-222; beta-CN, f 62-63, f 157-158, and f 205-206), Val-Tyr-Pro (beta-CN; f 59-61), and Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro (beta-CN; f 80-90). Chemical synthesis of these six peptides confirmed that all peptides, except an undecapeptide, have antihypertensive activity in spontaneously hypertensive rats. The synthetic tripeptide Ile-Pro-Ala, originating from beta-lactoglobulin, showed the strongest antihypertensive activity (-31 mm Hg).
Abubakar
A
A
Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Saito
T
T
Kitazawa
H
H
Kawai
Y
Y
Itoh
T
T
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002364:Caseins / Q000737:chemistry; D002611:Cheese / Q000032:analysis*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D019286:Endopeptidase K / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy; D007782:Lactoglobulins / Q000737:chemistry; D008297:Male; D008894:Milk Proteins / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D000067816:Whey Proteins; D001613:beta 2-Microglobulin / Q000737:chemistry
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002364:Caseins; D007782:Lactoglobulins; D008894:Milk Proteins; D010455:Peptides; D000067816:Whey Proteins; D001613:beta 2-Microglobulin; D010450:Endopeptidases; D019286:Endopeptidase K