Characterization of Angiotensin-Converting Enzyme Inhibitory Activity of X-Hyp-Gly-Type Tripeptides

Importance of Collagen-Specific Prolyl Hydroxylation

Yuki Taga, Osamu Hayashida, Ahmed Ashour, Yhiya Amen, Masashi Kusubata, Kiyoko Ogawa-Goto, Kuniyoshi Shimizu, Shunji Hattori

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Hydroxyproline (Hyp) is a collagen-specific amino acid formed by post-translational hydroxylation of Pro residues. Various Hyp-containing oligopeptides are transported into the blood at high concentrations after oral ingestion of collagen hydrolysate. Here we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of X-Hyp-Gly-type tripeptides. In an in vitro assay, ginger-degraded collagen hydrolysate enriched with X-Hyp-Gly-type tripeptides dose-dependently inhibited ACE and various synthetic X-Hyp-Gly-type tripeptides showed ACE-inhibitory activity. In particular, strong inhibition was observed for Leu-Hyp-Gly, Ile-Hyp-Gly, and Val-Hyp-Gly with IC50 values of 5.5, 9.4, and 12.8 μM, respectively. Surprisingly, substitution of Hyp with Pro dramatically decreased inhibitory activity of X-Hyp-Gly, indicating that Hyp is important for ACE inhibition. This finding was supported by molecular docking experiments using Leu-Hyp-Gly/Leu-Pro-Gly. We further demonstrated that prolyl hydroxylation significantly enhanced resistance to enzymatic degradation by incubation with mouse plasma. The strong ACE-inhibitory activity and high stability of X-Hyp-Gly-type tripeptides highlight their potential for hypertension control.

元の言語英語
ページ(範囲)8737-8743
ページ数7
ジャーナルJournal of Agricultural and Food Chemistry
66
発行部数33
DOI
出版物ステータス出版済み - 8 22 2018

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tripeptides
Hydroxylation
hydroxyproline
Hydroxyproline
peptidyl-dipeptidase A
Enzyme activity
hydroxylation
Peptidyl-Dipeptidase A
collagen
Collagen
Enzyme inhibition
hydrolysates
Ginger
oligopeptides
Oligopeptides
enzyme inhibition
ginger
hypertension
Inhibitory Concentration 50
inhibitory concentration 50

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

これを引用

Characterization of Angiotensin-Converting Enzyme Inhibitory Activity of X-Hyp-Gly-Type Tripeptides : Importance of Collagen-Specific Prolyl Hydroxylation. / Taga, Yuki; Hayashida, Osamu; Ashour, Ahmed; Amen, Yhiya; Kusubata, Masashi; Ogawa-Goto, Kiyoko; Shimizu, Kuniyoshi; Hattori, Shunji.

:: Journal of Agricultural and Food Chemistry, 巻 66, 番号 33, 22.08.2018, p. 8737-8743.

研究成果: ジャーナルへの寄稿記事

Taga, Yuki ; Hayashida, Osamu ; Ashour, Ahmed ; Amen, Yhiya ; Kusubata, Masashi ; Ogawa-Goto, Kiyoko ; Shimizu, Kuniyoshi ; Hattori, Shunji. / Characterization of Angiotensin-Converting Enzyme Inhibitory Activity of X-Hyp-Gly-Type Tripeptides : Importance of Collagen-Specific Prolyl Hydroxylation. :: Journal of Agricultural and Food Chemistry. 2018 ; 巻 66, 番号 33. pp. 8737-8743.
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abstract = "Hydroxyproline (Hyp) is a collagen-specific amino acid formed by post-translational hydroxylation of Pro residues. Various Hyp-containing oligopeptides are transported into the blood at high concentrations after oral ingestion of collagen hydrolysate. Here we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of X-Hyp-Gly-type tripeptides. In an in vitro assay, ginger-degraded collagen hydrolysate enriched with X-Hyp-Gly-type tripeptides dose-dependently inhibited ACE and various synthetic X-Hyp-Gly-type tripeptides showed ACE-inhibitory activity. In particular, strong inhibition was observed for Leu-Hyp-Gly, Ile-Hyp-Gly, and Val-Hyp-Gly with IC50 values of 5.5, 9.4, and 12.8 μM, respectively. Surprisingly, substitution of Hyp with Pro dramatically decreased inhibitory activity of X-Hyp-Gly, indicating that Hyp is important for ACE inhibition. This finding was supported by molecular docking experiments using Leu-Hyp-Gly/Leu-Pro-Gly. We further demonstrated that prolyl hydroxylation significantly enhanced resistance to enzymatic degradation by incubation with mouse plasma. The strong ACE-inhibitory activity and high stability of X-Hyp-Gly-type tripeptides highlight their potential for hypertension control.",
author = "Yuki Taga and Osamu Hayashida and Ahmed Ashour and Yhiya Amen and Masashi Kusubata and Kiyoko Ogawa-Goto and Kuniyoshi Shimizu and Shunji Hattori",
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T2 - Importance of Collagen-Specific Prolyl Hydroxylation

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AU - Hayashida, Osamu

AU - Ashour, Ahmed

AU - Amen, Yhiya

AU - Kusubata, Masashi

AU - Ogawa-Goto, Kiyoko

AU - Shimizu, Kuniyoshi

AU - Hattori, Shunji

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N2 - Hydroxyproline (Hyp) is a collagen-specific amino acid formed by post-translational hydroxylation of Pro residues. Various Hyp-containing oligopeptides are transported into the blood at high concentrations after oral ingestion of collagen hydrolysate. Here we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of X-Hyp-Gly-type tripeptides. In an in vitro assay, ginger-degraded collagen hydrolysate enriched with X-Hyp-Gly-type tripeptides dose-dependently inhibited ACE and various synthetic X-Hyp-Gly-type tripeptides showed ACE-inhibitory activity. In particular, strong inhibition was observed for Leu-Hyp-Gly, Ile-Hyp-Gly, and Val-Hyp-Gly with IC50 values of 5.5, 9.4, and 12.8 μM, respectively. Surprisingly, substitution of Hyp with Pro dramatically decreased inhibitory activity of X-Hyp-Gly, indicating that Hyp is important for ACE inhibition. This finding was supported by molecular docking experiments using Leu-Hyp-Gly/Leu-Pro-Gly. We further demonstrated that prolyl hydroxylation significantly enhanced resistance to enzymatic degradation by incubation with mouse plasma. The strong ACE-inhibitory activity and high stability of X-Hyp-Gly-type tripeptides highlight their potential for hypertension control.

AB - Hydroxyproline (Hyp) is a collagen-specific amino acid formed by post-translational hydroxylation of Pro residues. Various Hyp-containing oligopeptides are transported into the blood at high concentrations after oral ingestion of collagen hydrolysate. Here we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of X-Hyp-Gly-type tripeptides. In an in vitro assay, ginger-degraded collagen hydrolysate enriched with X-Hyp-Gly-type tripeptides dose-dependently inhibited ACE and various synthetic X-Hyp-Gly-type tripeptides showed ACE-inhibitory activity. In particular, strong inhibition was observed for Leu-Hyp-Gly, Ile-Hyp-Gly, and Val-Hyp-Gly with IC50 values of 5.5, 9.4, and 12.8 μM, respectively. Surprisingly, substitution of Hyp with Pro dramatically decreased inhibitory activity of X-Hyp-Gly, indicating that Hyp is important for ACE inhibition. This finding was supported by molecular docking experiments using Leu-Hyp-Gly/Leu-Pro-Gly. We further demonstrated that prolyl hydroxylation significantly enhanced resistance to enzymatic degradation by incubation with mouse plasma. The strong ACE-inhibitory activity and high stability of X-Hyp-Gly-type tripeptides highlight their potential for hypertension control.

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