血管紧张素转化酶抑制肽的研究进展

血管紧张素转化酶 (angiotensin I convertingenzyme ,ACE)在血压调节方面起着重要的作用 ,当其受到抑制时血压就会降低。许多合成的ACE抑制剂被广泛地应用于临床 ,但会造成多种副作用。近年来 ,对天然ACE抑制肽的研究表明 ,一些来源于蛋白酶解产生的活性肽可以对ACE起到有效的抑制作用。综述了血管紧张素转化酶的抑制肽的降压原理 ,种类和来源以及结构特点等的研究进展 ,并对其应用前景进行了展望。     

Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Bonito Bowels Autolysate

Six angiotensin I-converting enzyme inhibitory peptides were isolated from a bonito bowels autolysate. Their amino acids were sequenced as Tyr-Arg-Pro-Tyr, Gly-His-Phe, Val-Arg-Pro, Ile-Lys-Pro, Leu-Arg-Pro, and Ile-Arg-Pro. Peptides having corresponding amino acid sequences were synthesized by a solid-phase method and their inhibition of the activity measured. IC₅₀ of these peptides were estimated to be 320, 1100, 2.2, 2.5, 1.0, and 1.8 μM, respectively. The role of carboxyl terminal proline residues on the inhibition is discussed.     

Identification and Inhibitory Mechanism of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Bovine Hemoglobin

Angiotensin I-converting enzyme (ACE, EC.3.4.15.1) inhibitory peptide is an efficacious therapy for hypertension. In this study, four dipeptides, TY, FD, FL and FG, were identified from the desalted fraction of bovine hemoglobin hydrolysate, obtained by in vitro simulated gastrointestinal digestion, via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The IC₅₀ value of TY and FL are 96.43?±?6.17 and 290.66?±?57.92 μM, respectively. The result of molecular docking indicated that TY occupied the ACE subsite S1 and S1′ with a lowest estimated binding energy of ?9.96 Kcal/mol, while FL occupied the subsite S5 with a lowest estimated binding energy of ?9.37 Kcal/mol. The subsite S1′ and S2′ are closer to the ACE active center (Zn²⁺) than S5, and the lowest estimated binding energy of TY is lower than that of FL. This work provided new ACE-inhibitory peptides derived from bovine hemoglobin hydrolysate and explained their inhibitory mechanism.     

食品蛋白质中血管紧张素转化酶抑制肽的研究

血管紧张素转化酶Ⅰ (angiotensinIconvertingenzyme ,简称ACE)在人体血压调节过程中起重要的生理作用。源于食品蛋白质中的血管紧张素转化酶抑制肽 (angiotensinIconvertingenzymeinhibitorypeptides ,简称ACEIP)有明显的降血压作用 ,这些肽是通过抑制ACE的活性起降血压作用。文章中综述了来源于各种食品蛋白质的ACEIP的最新研究进展以及两种主要制备方法和评价方法 ,并对食品蛋白质中ACEIP的应用前景进行了展望     

Purification and Production of Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Bioactive Peptides Derived from Fermented Goat Milk

International Journal of Peptide Research and Therapeutics - In the study, five different Lactobacillus cultures i.e. L. rhamnosus (NK2) (KR080695), L. casei (NK9) (KR732325), L. fermentum (M5)...     

Novel Dipeptidyl Peptidase IV Inhibitory and Antioxidant Peptides Derived from Human Gastrointestinal Endogenous Proteins

Human gastrointestinal endogenous proteins (GEP) include the proteins mucins, serum albumin, digestive enzymes, and proteins from sloughed epithelial and microbial-cells. GEP play a vital role in the digestion of food, but are also simultaneously digested by proteases and peptidases of the gastrointestinal tract (GIT). Recent studies suggest that during gastrointestinal digestion, similar to dietary proteins, GEP may also give rise to bioactive peptides. In the present study, the protein sequences of 11 representative GEP were subjected to simulated in silico GIT (SIGIT) digestion. Following SIGIT digestion, 19 novel GEP-derived peptide sequences were selected using quantitative structure activity relationship rules for chemical synthesis. The peptides were then tested for their in vitro dipeptidyl peptidase IV (DPP-IV) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition, and for their ferric reducing antioxidant power (FRAP). Two novel DPP-IV inhibitory peptides with the amino acid sequences RPCF (IC₅₀ = 800.51 ± 49.00 µM) and MIM (IC₅₀ = 1056.78 ± 61.11 µM), and five novel antioxidant peptides CCK, RPCF, CRPK, QQCP and DCR were identified. The results of this study indicate that GEP are a significant source of bioactive peptides with potential novel bioactive peptide fragments within their sequences.     

Activity Prediction and Molecular Mechanism of Bovine Blood Derived Angiotensin I-Converting Enzyme Inhibitory Peptides

Development of angiotensin I-converting enzyme (ACE, EC 3.4.15.1) inhibitory peptides from food protein is under extensive research as alternative for the prevention of hypertension. However, it is difficult to identify peptides released from food sources. To accelerate the progress of peptide identification, a three layer back propagation neural network model was established to predict the ACE-inhibitory activity of pentapeptides derived from bovine hemoglobin by simulated enzyme digestion. The pentapeptide WTQRF has the best predicted value with experimental IC₅₀ 23.93 μM. The potential molecular mechanism of the WTQRF / ACE interaction was investigated by flexible docking.     

In Silico Evaluation of Food Derived Bioactive Peptides as Inhibitors of Angiotensin Converting Enzyme (ACE)

International Journal of Peptide Research and Therapeutics - Hypertension is declared as the major risk factor of cardiovascular diseases and stroke, and the leading cause of premature deaths. ACE...     

Correction to: In Silico Evaluation of Food Derived Bioactive Peptides as Inhibitors of Angiotensin Converting Enzyme (ACE)

International Journal of Peptide Research and Therapeutics - The original version of the article unfortunately contained a typo in co-author name.     

Relationship between the Unicellular Red Alga Porphyridium sp. and Its Predator, the Dinoflagellate Gymnodinium sp

Contamination of algae cultivated outdoors by various microorganisms, such as bacteria, fungi, algae, and protozoa, can affect growth and product quality, sometimes causing fast collapse of the cultures. The main contaminant of Porphyridium cultures grown outdoors in Israel is a Gymnodinium sp., a dinoflagellate that feeds on the alga. Comparison of the effects of various environmental conditions, i.e., pH, salinity, and temperature, on Gymnodinium and Porphyridium species revealed that the Gymnodinium sp. has sharp optimum curves, whereas the Porphyridium sp. has a wider range of optimum conditions and is also more resistant to extreme environmental variables. The mode of preying on the alga was observed, and the specificity of the Gymnodinium sp. for the Porphyridium sp. was shown. In addition, Gymnodinium extract was shown to contain enzymatic degrading activity specific to the Porphyridium sp. cell wall polysaccharide.     

Photochemical Performance of the Acidophilic Red Alga Cyanidium sp. in a pH Gradient

The acidophilic red alga Cyanidium sp. is one of the dominant mat-forming species in the highly acidic waters of Río Tinto, Spain. The culture of Cyanidium sp., isolated from a microbial mat sample collected at Río Tinto, was exposed to 9 different pH conditions in a gradient from 0.5 to 5 for 24?h and its physiological status evaluated by variable chlorophyll a fluorescence kinetics measurements. Maximum quantum yield was determined after 30?min, 1?h, 2?h, 4?h, 6?h and 24?h of exposure after 15?min dark adaptation. The effect of pH on photochemical activity of Cyanidium sp. was observable as early as 30?min after exposure and the pattern remained stable or with only minor modifications for 24?h. The optimum pH ranged from 1.5 to 2.5. A steep decrease of the photochemical activity was observed at pH below 1 even after 30?min of exposure. Although the alga had tolerated the exposure to pH?=?1 for at least 6?h, longer (24?h) exposure resulted in reduction of the photochemical activity. At pH above 2.5, the decline was more moderate and its negative effect on photochemistry was less severe. According to the fluorescence measurements, the red alga Cyanidium sp. is well-adapted to prevailing pH at its original locality at Río Tinto, i.e. pH of 1 to 3. The short-term survival in pH?相似文献   

Screening of Surface-associated Bacteria from the Mexican Red Alga Halymenia floresii for Quorum Sensing Activity

Microbiology - Macroalgae host a dense bacterial epibiome forming surface biofilms, which act as a biological defense by protecting the surface from macrofoulers. During experimental cultivation of...     

Inhibitory Effects of Secondary Metabolites from the Red Alga Delisea pulchra on Swarming Motility of Proteus mirabilis

Abnormal, uncoordinated swarming motility of the opportunistic human pathogen Proteus mirabilis was seen when a crude extract of the Australian red alga Delisea pulchra was added to the medium. This occurred at concentrations at which growth rate, swimming motility, cell elongation, polynucleation, and hyperflagellation were not affected. One halogenated furanone from D. pulchra inhibited swarming motility at concentrations that did not affect growth rate and swimming motility. Other structurally similar D. pulchra furanones had no effect on swarming, suggesting considerable specificity in the effects of furanones on swarming motility by P. mirabilis.     

Identification and Characterization of Novel Lipophilic Antimicrobial Peptides Derived from Naturally Occurring Proteins

Microbes are increasingly developing defensive mechanisms against known drugs via mutations. There are signs of emergence of superbugs immune to most known antibiotics available. The need for a new class of drugs to counteract this problem is of paramount importance for continued general well being of mankind. A new class of drugs, antimicrobial peptides, has not been fully exploited primarily due to high cytotoxicity, poor lipophilicity preventing systemic distribution and stability. We have synthesised 9-amino acid residue cationic peptides RH01 and RH02 lipidated with myristoyl and octyl groups respectively. These peptides exhibited potent antimicrobial activity and low cytotoxicity. The lipopeptide RH01 has antimicrobial activity against a broad range of microorganisms including bacteria, yeast and filamentous fungi with greatest activity toward Gram-positive bacteria, including S. aureus MRSA stain, MIC’s ranging between 2–8 μM. The MIC for Gram-negative bacteria was higher ranging from between 30–250 μM. RH01 also had antimicrobial activity towards fungi showing good activity against the pathogenic yeast Candida albicans but was less active towards the filamentous fungi Aspergillus niger. The antimicrobial activity of RH01 as a measure of Ki₍₅₀₎ for E. coli and S. aureus was 35–60 μM and 3–7 μM, respectively. In-house data showed the compound is bactericidal even at higher bacteria concentration. The octylated lipopeptide RH02 has similar activities towards S. aureus (3.3 μM) and E coli (53.3 μM) as the myristolated RH01. There was no haemolytic activity of the lipopeptide RH01 towards human blood. Acute intravenous toxicity study in mice showed that both RH01 and RH02 induced no macroscopic abnormalities at their highest non-lethal dose of 75 mg/kg and 150 mg/kg bodyweight, respectively.Australian Peptide Conference Issue.     

Kinetics Study of Protein Hydrolysis and Inhibition of Angiotensin Converting Enzyme by Peptides Hydrolysate Extracted from Walnut

Bioactive peptides are defined as protein-based components having nutritional value and have proved roles important for the human health. In this study inhibition of angiotensin converting enzyme (ACE) by protein-based hydrolysate extracted from walnut (Juglanse regia. L.) seeds was evaluated. The peptide fraction obtained by enzymatic hydrolysis with trypsin showed higher ACE-inhibitory and lower IC₅₀ value (0.39?±?0.05 mg/mL) than obtained by hydrolysis with chymotrypsin and proteinase K. The study of kinetics showed that by increasing the concentration of the trypsin hydrolysate from 0.01–0.5 mg/mL, K_m increased, while V_max decreased. Also the value of K_i was found to be 0.17?±?0.01 mg/mL, which means that binding affinity for the substrate decreased in the presence of inhibitor. The structural studies of ACE demonstrated that, in comparison with a commercial antihypertension drug (enalapril), the trypsin hydrolysate had no effect on secondary structure and less tertiary structure changes of protein was observed.     

Cytokinins from the tRNA of the Red Alga Porphyra perforata J. Ag.

Isopentenyladenosine and cis-zeatin riboside have been identifiedby GC-MS from the tRNA of a red alga Porphyra perforata. (Received March 12, 1991; Accepted December 7, 1991)     

Carbonic Anhydrase of a Unicellular Red Alga Porphyridium cruentum R-l. I. Purification and Properties of the Enzyme

Cells of Porphyridium cruentum R-l, a unicellular red alga,grown under ordinary air (0.04% CO₂) showed much higher activityof carbonic anhydrase (CA) than those grown under CCvenrichedair (2% CO₂). CA activity was not detected in a suspension ofintact cells, and was detectable only after the cells had beenhomogenized, indicating that this enzyme was localized onlywithin the algal cells. After partial purification of Porphyridium CA, its mol wt wasestimated as 59 kDa by SDS-PAGE and 55 kDa by gelfiltration.This suggests that the native enzyme is a monomer. Its activitywas not affected by benzensulfonamides, potent inhibitors ofCAs isolated from Chlamydomonas and other organisms. Chloride(or bromide) ions was essential for CA activity. CA activitymarkedly decreased when the cell extract had been incubatedat pH lower than 7 before assay. Upon readjusting the pH ofthe preincubation medium to 9 or higher, the enzyme activitywas restored, indicating that the inactivation is reversible. (Received April 17, 1987; Accepted July 21, 1987)     

Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme,N-Deacetylase-N-sulfotransferase-1

N-Deacetylase-N-sulfotransferase 1 (Ndst1) catalyzes the initial modification of heparan sulfate and heparin during their biosynthesis by removal of acetyl groups from subsets of N-acetylglucosamine units and subsequent sulfation of the resulting free amino groups. In this study, we used a phage display library to select peptides that interact with Ndst1, with the aim of finding inhibitors of the enzyme. The phage library consisted of cyclic random 10-mer peptides expressed in the phage capsid protein pIII. Selection was based on the ability of engineered phage to bind to recombinant murine Ndst1 (mNdst1) and displacement with heparin. Peptides that were enriched through multiple cycles of binding and disassociation displayed two specific sequences, CRGWRGEKIGNC and CNMQALSMPVTC. Both peptides inhibited mNdst1 activity in vitro, however, by distinct mechanisms. The peptide CRGWRGEKIGNC presents a chemokine-like repeat motif (BXX, where B represents a basic amino acid and X is a noncharged amino acid) and binds to heparan sulfate, thus blocking the binding of substrate to the enzyme. The peptide NMQALSMPVT inhibits mNdst1 activity by direct interaction with the enzyme near the active site. The discovery of inhibitory peptides in this way suggests a method for developing peptide inhibitors of heparan sulfate biosynthesis.     

CuZn-Superoxide Dismutases from the Fern Equisetum arvense and the Green Alga Spirogyra sp.: Occurrence of Chloroplast and Cytosol Types of Enzyme

CuZn-superoxide dismutase (SOD) from horsetail (Equisetum arvense)was purified to a crystalline state and that from pond scum(Spirogyra sp.) was purified to a mixture of three isozymes.The purified CuZn-SODs from the fern and the green alga showsimilar properties to those of the angiosperm and mammalianenzymes with respect to molecular weight, subunit structure,absorption spectrum, circular dichroism spectrum and the effectof modification of the arginine residues by 2,3-butanedioneon activity. Horsetail and pond scum contained three isozymeseach of CuZn-SOD. These isozymes are divided to two types: onetype gave a cross-reaction with antibody raised against chloroplast-typeCuZn-SOD from spinach and other type cross-reacted with antibodyraised against cytosol-type CuZn-SOD from spinach. Thus, itappears that the divergence of the chloroplast and cytosol typesof CuZn-SOD started at a very early stage in the molecular evolutionof this enzyme. (Received January 30, 1989; Accepted April 19, 1989)     

A Highly N-Glycosylated Chitin Deacetylase Derived from a Novel Strain of Mortierella sp. DY-52

Chitin deacetylase (CDA), the enzyme that catalyzes the hydrolysis of acetamido groups of GlcNAc in chitin, was purified from culture filtrate of the fungus Mortierella sp. DY-52 and characterized. The extracellular enzyme is likely to be a highly N-glycosylated protein with a pI of 4.2–4.8. Its apparent molecular weight was determined to be about 52 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS–PAGE) and 67 kDa by size-exclusion chromatography. The enzyme had an optimum pH of 6.0 and an optimum temperature of 60 °C. Enzyme activity was slightly inhibited by 1–10 mM Co²⁺ and strongly inhibited by 10 mM Cu²⁺. It required at least two GlcNAc residues for catalysis. When (GlcNAc)₆ was used as substrate, K _m and V _max were determined to be 1.1 mM and 54.6 μmol min^?1 respectively.