Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cathepsin B is a lysosomal cysteine protease exhibiting mainly dipeptidyl carboxypeptidase activity, which decreases dramatically above pH 5.5, when the enzyme starts acting as an endopeptidase. Since the common cathepsin B assays are performed at pH 6 and do not distinguish between these activities, we synthesized a series of peptide substrates specifically designed for the carboxydipeptidase activity of cathepsin B. The amino-acid sequences of the P(5)-P(1) part of these substrates were based on the binding fragments of cystatin C and cystatin SA, the natural reversible inhibitors of papain-like cysteine protease. The sequences of the P'(1)-P'(2) dipeptide fragments of the substrates were chosen on the basis of the specificity of the S'(1)-S'(2) sites of the cathepsin B catalytic cleft. The rates of hydrolysis by cathepsin B and papain, the archetypal cysteine protease, were monitored by a continuous fluorescence assay based on internal resonance energy transfer from an Edans to a Dabcyl group. The fluorescence energy donor and acceptor were attached to the C- and the N-terminal amino-acid residues, respectively. The kinetics of hydrolysis followed the Michaelis-Menten model. Out of all the examined peptides Dabcyl-R-L-V-G-F- E(Edans) turned out to be a very good substrate for both papain and cathepsin B at both pH 6 and pH 5. The replacement of Glu by Asp turned this peptide into an exclusive substrate for cathepsin B not hydrolyzed by papain. The substitution of Phe by Nal in the original substrate caused an increase of the specificity constant for cathepsin B at pH 5, and a significant decrease at pH 6. The results of kinetic studies also suggest that Arg in position P(4) is not important for the exopeptidase activity of cathepsin B, and that introducing Glu in place of Val in position P(2) causes an increase of the substrate preference towards this activity.
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PMID:Fluorogenic peptide substrates for carboxydipeptidase activity of cathepsin B. 1509 28

Some of the most potent ACE-inhibitory peptides described in food have a proline at the end of their sequence, a characteristic that can cause problems in the synthesis procedures. In this work, we studied two different preparations of peptide Asp-Lys-Ile-His-Pro (DKIHP), which were obtained by two different synthetic procedures (Boc and Fmoc). The peptide synthesized by the Boc method yielded a unique conformer, containing trans-Pro, and significant ACE-inhibitory activity (IC(50) = 113.18 microM). The chromatographic and NMR data of this active conformer are reported. The peptide synthesized by Fmoc chemistry yielded three conformers, two of them containing trans-Pro and a third one containing cis-Pro, and showed a lower activity (IC(50) = 577.92 microM). This was attributed to the presence of conformers with less (or none) activity. We have pointed out the importance of performing structural studies on these type of peptides before testing their ACE-inhibitory activity.
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PMID:ACE-inhibitory activity and structural properties of peptide Asp-Lys-Ile-His-Pro [beta-CN f(47-51)]. Study of the peptide forms synthesized by different methods. 1545 6

It is well established that renin-angiotensin system (RAS) is the major regulatory network that maintains blood pressure, fluid and electrolyte balance and the homeostasis of cardiovascular system. Most studies in the last decades centered on the pivotal members of RAS, that is, angiotensin II (Ang II ) and angiotensin converting enzyme (ACE). Recent identification of ACE-2, the homology of ACE, and the identification of the multiple products degraded from angiotensin I, including Ang III, Ang IV, Ang(1-9), Ang(1-7), Des-Asp-angiotensin I(DAA I), etc, have proved that Ang II is not the only biological active compound of RAS. Peptides derived from angiotensinogen,that is, family of angiotensins,display independent and pleiotropic biological activities in vivo, and interact with each other both in metabolism pathway and the biologic effects. The imbalance of the network of angiotensin metabolites exhibits significant pathophysiological role in cardiovascular disease.
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PMID:[Family of multiple peptide fragments derived from angiotensin and their interaction]. 1637 26

Discovery of the chemical structure of alligator (Alligator mississipiensis) [Asp(1), Val(5), Ala(9)]-Angiotensin I (ANG I) has permitted the investigation of cardiovascular responses to this peptide and its analogs in spectacled caimans (Caiman crocodilus), close relatives of alligators. ANG I and [Asp(1), Val(5)]- Angiotensin II (ANG II) i.v. gave dose-dependent increases in mean arterial pressure but there was no pressor response to [Val(4)]-ANG III (ANG III). Pressor responses to a series of doses of ANG II were compared with a range of doses of norepinephrine (NE) and epinephrine (E) which were found to be only about 1/100 as potent as ANG II on a molar basis. The replacement of d-leu(10)in the alligator ANG I molecule with l-leu(10) almost stopped its conversion to ANG II and attenuated the pressor response. [Asp(1), Val(5), Ala(9)]-ANG I (1-9), and ANG (1-7) both failed to increase arterial blood pressure, even at the relatively high non-physiological test dose of 194pmolkgbw(-1) i.v. Captopril blocked angiotensin converting enzyme (ACE) and prevented the pressor response to ANG I whereas the mammalian AT(1) inhibitor Losartan attenuated, but did not completely block the pressor response to ANG II. These are the first experiments which test the cardiovascular responses to alligator ANG I and its analogues in any crocodilian species.
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PMID:Pressor responses to alligator Angiotensin I and some analogs in the spectacled caiman (Caiman crocodilus). 1649 78

Mung bean protein isolates were hydrolyzed for 2 h by Alcalase. The generated hydrolysate showed angiotensin I-converting enzyme (ACE) inhibitory activity with the IC(50) value of 0.64 mg protein/ml. Three kinds of novel ACE inhibitory peptides were isolated from the hydrolysate by Sephadex G-15 and reverse-phase high performance liquid chromatography (RP-HPLC). These peptides were identified by amino acid composition analysis and matrix assisted-laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS), as Lys-Asp-Tyr-Arg-Leu, Val-Thr-Pro-Ala-Leu-Arg and Lys-Leu-Pro-Ala-Gly-Thr-Leu-Phe with the IC(50) values of 26.5 microM, 82.4 microM and 13.4 microM, respectively.
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PMID:Novel angiotensin I-converting enzyme inhibitory peptides isolated from Alcalase hydrolysate of mung bean protein. 1668 Jul 98

There have been studies of antihypertensive peptides derived from food proteins, but very few described the production of bioactive peptides from egg proteins. The first 2 antihypertensive peptides isolated in egg were obtained by enzymatic hydrolysis of ovalbumin. They correspond to the sequences Phe-Arg-Ala-Asp-His-Pro-Phe-Leu (ovokinin) and Arg-Ala-Asp-His-Phe-Leu (ovokinin 2-7). Both exhibited endothelium-dependent vasodilatory activity. Ovokinin (2-7) had higher antihypertensive potency than ovokinin in spontaneously hypertensive rats (SHR). Modifications in the sequence of ovokinin (2-7) improved the bioavailability of this peptide. It was also demonstrated that different ovalbumin hydrolysates can inhibit angiotensin I-converting enzyme (ACE). We recently obtained an egg white hydrolysate that inhibited the enzyme in vitro. It was obtained by treating egg white with pepsin and it exhibited antihypertensive activity in SHR. Some ACE-inhibitory peptides obtained from this hydrolysate (Tyr-Arg-Glu-Glu-Arg-Tyr-Pro-Ile-Leu, Arg-Ala-Asp-His-Pro-Phe-Leu, and Ile-Val-Phe) also showed antihypertensive activity in these rats. The egg products mentioned could be used as functional food ingredients with potential therapeutic benefit in the prevention and treatment of hypertension.
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PMID:Antihypertensive peptides derived from egg proteins. 1670 3

Blockade of the renin-angiotensin system (RAS) with angiotensin I-converting enzyme (ACE) inhibitors and AT1-receptor (AT1R) blockers has become one of the most successful therapeutic approaches in medicine. The question is no longer whether RAS inhibition helps, but rather how we can optimize inhibition to achieve optimal cardiovascular and renal protection. Indeed, numerous data have shown that the RAS is not blocked fully over 24 hours with current doses of RAS blockers because they trigger a counter-regulatory renin release that can offset pharmacologic inhibition of the RAS. This absence of full blockade may have clinical implications. Combination therapy with ACE inhibitors and AT1R antagonists thus has been proposed to inhibit the biological effects of the reactive renin release triggered by single-site RAS inhibition. By using this approach, numerous experimental and clinical studies have suggested that this combination therapy has additive or synergistic effects on blood pressure and on the prevention of cardiovascular and renal lesions. Although similar intensity of RAS blockade can be achieved by either combination therapy or by using high doses of an AT1-receptor antagonist given alone, the ACE inhibitor present in the combination interferes with the bradykinin-nitric oxide pathway and the N-acetyl-Ser-Asp-Lys-Pro metabolism, which both may have additional biological effects.
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PMID:Rationale for combining blockers of the renin-angiotensin system. 1786 92

In the search for novel peptides that inhibit the angiotensin I-converting enzyme (ACE), porcine skeletal troponin was hydrolyzed with pepsin, and the products were subjected to various types of chromatography to isolate active peptides. Glu-Lys-Glu-Arg-Glu-Arg-Gln (EKERERQ) and Lys-Arg-Gln-Lys-Tyr-Asp-Ile (KRQKYDI) were identified as active peptides, and their 50% inhibitory concentrations were found to be 552.5 and 26.2 microM, respectively. These are novel ACE inhibitory peptides, and the activity of KRQKYDI was the strongest among previously reported troponin-originated peptides. KRQKYDI was slowly hydrolyzed by treatment with ACE, and kinetic studies indicated that this peptide was a competitive inhibitor of the enzyme. When KRQKYDI was administered orally to spontaneously hypertensive rats (SHR) at a dose of 10 mg/kg, a temporary antihypertensive activity was observed at 3 and 6 h after administration.
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PMID:Porcine skeletal muscle troponin is a good source of peptides with Angiotensin-I converting enzyme inhibitory activity and antihypertensive effects in spontaneously hypertensive rats. 1816 67

High blood pressure (HBP) is an important risk factor for cardiac, renal, and vascular dysfunction. Excess inflammation is the major pathogenic mechanism for HBP-induced target organ damage (TOD). N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a tetrapeptide specifically degraded by angiotensin converting enzyme (ACE), reduces inflammation, fibrosis, and TOD induced by HBP. Our hypothesis is that Ac-SDKP exerts its anti-inflammatory effects by inhibiting: 1) differentiation of bone marrow stem cells (BMSC) to macrophages, 2) activation and migration of macrophages, and 3) release of the proinflammatory cytokine TNF-alpha by activated macrophages. BMSC were freshly isolated and cultured in macrophage growth medium. Differentiation of murine BMSC to macrophages was analyzed by flow cytometry using F4/80 as a marker of macrophage maturation. Macrophage migration was measured in a modified Boyden chamber. TNF-alpha release by activated macrophages in culture was measured by ELISA. Myocardial macrophage activation in mice with ANG II-induced hypertension was studied by Western blotting of Mac-2 (galectin-3) protein. Interstitial collagen deposition was measured by picrosirius red staining. We found that Ac-SDKP (10 nM) reduced differentiation of cultured BMSC to mature macrophages by 24.5% [F4/80 positivity: 14.09 +/- 1.06 mean fluorescent intensity for vehicle and 10.63 +/- 0.35 for Ac-SDKP; P < 0.05]. Ac-SDKP also decreased galectin-3 and macrophage colony-stimulating factor-dependent macrophage migration. In addition, Ac-SDKP decreased secretion of TNF-alpha by macrophages stimulated with bacterial LPS. In mice with ANG II-induced hypertension, Ac-SDKP reduced expression of galectin-3, a protein produced by infiltrating macrophages in the myocardium, and interstitial collagen deposition. In conclusion, this study demonstrates that part of the anti-inflammatory effect of Ac-SDKP is due to its direct effect on BMSC and macrophage, inhibiting their differentiation, activation, and cytokine release. These effects explain some of the anti-inflammatory and antifibrotic properties of Ac-SDKP in hypertension.
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PMID:Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage. 1817 15

Acetes chinensis is an underutilized shrimp species thriving in Bo Hai Gulf of China. Its hydrolysate digested with protease SM98011 has been previously shown to have high angiotensin I-converting enzyme (ACE) inhibitory activity (He et al., J Pept Sci 12:726-733, 2006). In this article, A. chinensis were fermented by Lactobacillus fermentum SM 605 and the fermented sauce presented high ACE inhibitory activity. The minimum IC(50) value (3.37 +/- 0.04 mg/mL) was achieved by response surface methodology with optimized process parameters such as fermentation time of 24.19 h, incubation temperature at 38.10 degrees C, and pH 6.12. Three ACE inhibitory peptides are purified by ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. Identified by mass spectrometry, their amino acid sequences are Asp-Pro, Gly-Thr-Gly, and Ser-Thr, with IC(50) values of 2.15 +/- 0.02, 5.54 +/- 0.09, and 4.03 +/- 0.10 microM, respectively. Also, they are all novel ACE inhibitory peptides. Compared with protease digestion, fermentation is a simpler and cheaper method to produce ACE inhibitory peptides from shrimp A. chinensis.
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PMID:Production of novel angiotensin I-converting enzyme inhibitory peptides by fermentation of marine shrimp Acetes chinensis with Lactobacillus fermentum SM 605. 1852 93


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