Isolation of Acein‐2, a novel angiotensin‐I‐converting enzyme inhibitory peptide derived from a tryptic hydrolysate of human plasma

Abstract

We previously described a novel angiotensin-I-converting enzyme (ACE) inhibitory peptide, designated Acein-1, that was isolated from a tryptic hydrolysate of human plasma. We now report a second such inhibitory peptide, Acein-2 obtained from the same hydrolysate. The peptide was purified by gel filtration and cation exchange chromatography followed by reversed-phase gradient and isocratic high performance liquid chromatography. Acein-2 was found to be a tripeptide, Leu-IleTyr, which is thought to correspond to f(518^520) of human K K2-macroglobulin. The synthetic tripeptide showed a potent dosedependent inhibition of ACE, with an IC 50 value of 0.82 W Wmol/l. Lineweaver^Burk plots suggested that Acein-2 as well as the previously described Acein-1 are non-competitive inhibitors.z 2000 Federation of European Biochemical Societies.

Effects of hydrolysis and digestion in vitro on the activity of bovine plasma hydrolysates as inhibitors of the angiotensin I converting enzyme

“…It has been proved that the hydrophobic amino acids in this position favor the link of the peptide with the ACE (Vinderola et al 2008). The dipeptide AW was identified like a powerful ACEI (Nakagomi et al 2000). The peptides S1 and S2 possessed A in the tripeptide C-terminal sequence, which as mentioned above, favored the union of peptide with the ACE, and also had the presence of V in its sequence, amino acid predominant in ACEI peptides because of its hydrophobic amino acid nature.…”

“…However, because the ACE active site could not locate large peptide molecules, this was demonstrated by the means of crystallographic studies (Natesh et al 2003). Different ACEI peptides of blood protein of plasma have been previously isolated (Park and Song 1997;Nakagomi et al 2000;Wanasundara et al 2002;Lee and Song 2003). However, none of the identified peptide sequences in the peak Ic were found in the above mentioned studies, nor any of them were reported in BIOPEP data base, which comprised published information about the bioactive peptides and had 556 ACEI peptides sequences cureently.…”

Isolation of Novel Peptides, Cabin-1, -2, -3, and -4, That Inhibit Cathepsin B from a Thermolysin Digest of Human Plasma.

“…Many bioactive peptides have been isolated from enzymatic hydrolysates of proteins. [9][10][11][12][13][14][26][27][28][29] However, only a few peptides have so far been isolated from enzymatic hydrolysates of human proteins. Other than casoxin D (YVPFPPF), which was isolated from a peptic hydrolysate of human casein as a bradykinin agonist, 27) Acein-1, Acein-2, Ala-Trp, and human albutensin A, all of which are ACE inhibitory peptides, are the only peptides that have been isolated to our knowledge.…”

“…Other than casoxin D (YVPFPPF), which was isolated from a peptic hydrolysate of human casein as a bradykinin agonist, 27) Acein-1, Acein-2, Ala-Trp, and human albutensin A, all of which are ACE inhibitory peptides, are the only peptides that have been isolated to our knowledge. [10][11][12] Cabin-1, -2, -3, and -4 might be valuable because they are derived from enzymatic hydrolysates of human serum proteins, although the IC 50 values of these peptides were less than those of synthetic cathepsin B inhibitors such as E-64 (IC 50 3.4 nmol/l) and CA-074 (L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl)-Lisoleucyl-L-proline (IC 50 2.2 nmol/l). 30,31) The present results suggest that Cabin-1, -2, -3, and -4 could be used as new leads for anti-cathepsin B drugs, although it is not yet known whether these peptides are released from serum proteins by endogenous thermolysin-like enzymes in the human body to act as internal cathepsin B inhibition.…”

“…8) Several enzyme inhibitory peptides have also been isolated from enzymatic hydrolysates of proteins. [9][10][11][12][13][14] We previously isolated Acein-1 10) and Acein-2, 11) which are novel peptides that inhibit angiotensin I-converting enzyme (ACE). Acein-1 was isolated from a tryptic hydrolysate of human plasma with the amino acid sequence of Tyr-LeuTyr-Glu-Ile-Ala-Arg, which corresponds to f(138-144) of human serum albumin.…”