Peptide inhibitors for angiotensin I-converting enzyme from thermolysin digest of dried bonito.
Dried bonito (Katsuobusi), a Japanese traditional seasoning made of bonito muscle was hydrolyzed by various proteases and the inhibitory activity of the hydrolyzates for angiotensin I-converting enzyme (ACE) [EC 3.4.15.1] was measured. Among the digests, thermolysin digest showed the most potent inhibitory activity. Eight inhibitory peptides were isolated from the digest using HPLC. The amino acid sequences of inhibitory peptides were Ile-Lys-Pro-Leu-Asn-Tyr, Ile-Val-Gly-Arg-Pro-Arg-His-Gln-Gly, Ile-Trp-His-His-Thr, Ala-Leu-Pro-His-Ala, Phe-Gln-Pro, Leu-Lys-Pro-Asn-Met, Ile-Tyr, and Asp-Tyr-Gly-Leu-Tyr-Pro. By searching for the sequence homology in many proteins, four of them were found in the primary structure of actin. Asp-Met-Ile-Pro-Ala-Gln-Lys was obtained from the boiling water extract of dried bonito and this peptide was found in the primary structure of creatine kinase. Fragments of these peptides were prepared by further enzymatic digestion or chemical synthesis and their ACE-inhibitory activities were measured. Among them, Ile-Lys-Pro, Ile-Trp, Leu-Lys-Pro, and Leu-Tyr-Pro had higher inhibitory activity than their parental peptides. Ile-Lys-Pro suppressed the hypertensive activity of angiotensin I.
Yokoyama
K
K
Nippon Synthetic Chemical Industry Co., Ltd., Osaka, Japan.
Chiba
H
H
Yoshikawa
M
M
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D005396:Fish Products / Q000032:analysis*; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013820:Thermolysin / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D010455:Peptides; D010450:Endopeptidases; D013820:Thermolysin