Małgorzata Darewicz

Food‐Originating ACE Inhibitors, Including Antihypertensive Peptides, as Preventive Food Components in Blood Pressure Reduction

This work is a literature overview on angiotensin-converting enzyme (ACE) inhibitory/antihypertensive peptides in food protein sources. The following aspects related to peptides with the above-mentioned bioactivity are discussed: (i) mechanism of action of ACE, (ii) the structural character of ACE inhibitors/antihypertensive peptide sequences determined by different methods, including quantitative structure-activity relationship studies, (iii) their food sources, (iv) absorption of peptides, (v) in vitro and in vivo approaches involved in the production and potential release of peptide ACE inhibitors as well as in silico methods applied in research concerning peptides.

Food Proteins as Precursors of Bioactive Peptides — Classification Into Families

The Bioactive Peptides (BIOPEP) database developed at the Department of Food Biochemistry, University of Warmia and Mazury in Olsztyn was used to determine the profiles of the potential biological activity of food proteins and to classify them into families. Proteins whose amino acid sequences contained fragments with a specified activity and which were a potential source of this activity were divided into families. Among the 44 biological activities of peptides included in the BIOPEP database, 23 were selected for analysis. The number of families was diversified. The largest families were composed of proteins — precursors of antihypertensive peptides and dipeptidyl aminopeptidase IV inhibitors as well as those activating ubiquitin-mediated proteolysis and opioid ones. Only a few proteins included in the database contained in their sequences fragments with the following activities: chemotactic, binding and transporting metals and metal ions, stimulating red blood cells synthesis, inducing contractions of smooth muscles, and hemolytic. Highly numerous families were divided into five sub-families according to the value of the frequency of occurrence of fragments exhibiting given activity (A parameter).

Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar) Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE) inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes) and ex vivo digestion (with human gastrointestinal enzymes). Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50%) of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

The Preventive Potential of Milk and Colostrum Proteins and Protein Fragments

This study presents and analyzes the results of in silico, in vitro, and in vivo tests investigating the potential preventive properties of a group of biologically active milk and colostrum proteins and peptides; that is, casein, α-lactalbumin, β-lactoglobulin, lysozyme, lactoferrin, glycomacropeptide, proline-rich peptides, and lactoperoxidase. Casein or its peptides lowers blood pressure, reduces tumor growth, and shows anticoagulant, antimicrobial, and antioxidant activity. Casein hydrolysates decrease the probability of diabetes. α-Lactalbumin and β-lactoglobulin manifest antiviral activity directed against HIV and antibacterial and hypotensive activities. A diet rich in α-lactalbumin has antistress, antidepressive, and anticarcinogenic properties. Lysozyme is used as a supplement in infant formulas and an anti-inflammatory and analgesic agent in neoplastic diseases. Lactoferrin demonstrates an antibacterial, antiviral, fungistatic, antiparasitic, and antithrombotic effect. Glycomacropeptide is characterized by antibacterial, antiviral, and antithrombotic properties. Colostrinin, a proline-rich peptide, is applied in the treatment of neurodegenerative diseases of the brain and autoimmune diseases. Lactoperoxidase is an antimicrobial agent. Studies indicate that milk and colostrum proteins and peptides have many applications in the prevention and treatment of various diseases in patients from all age groups.

Computational Characterisation and Identification of Peptides for in silico Detection of Potentially Celiac-Toxic Proteins

This work reports on in silico analysis of celiac-toxic peptide occurrence in proteins. The toxic properties of celiac disease are linked to the presence of specific amino acid sequences and the properties of their environment. The analysed celiac-toxic peptides were found to be predominated by unordered structures of random coil and β-turns. Proline and glutamine-rich amino acid sequences from hydrophilic β-turns were exposed on the surface of the precursor proteins. The sequence motifs represented by gluten peptide epitopes or tetrapeptides with surroundings seem to represent an immunodominant structure. The application of MS BLAST software enabled identification of a few fragments with high degrees of identity to the toxic peptides in one protein sequence. Rich sources of celiac-disease-potentiating peptides were wheat gliadins, barley hordeins and rye secalins as well as low-molecular weight fractions of glutenin. In addition, amino acid sequences with a high degree of identity to the toxic peptides examined were detected in maize zein, oat avenin, protein of rice, yeast and chicken muscles, as well as β-casein and galanin.

BIOPEP database of sensory peptides and amino acids

Peptides and amino acids belong to compounds that influence the taste of foods. The aim of this study was to develop a database of sensory peptides and amino acids. Information about the taste of the analyzed compounds was obtained from sensory studies described in the literature. The database of sensory peptides and amino acids has identical structure to the BIOPEP database of biologically active peptides. The information about sensory peptides and amino acids was inserted into the database using standard BIOPEP layouts for bioactive peptides. Information about the biological activity of sensory peptides was obtained from BIOPEP and other databases. The information annotated in the BIOPEP database of sensory peptides and amino acids includes: sequence written in a one-letter code, information about taste, reference, structure written with the use of chemical codes (SMILES, InChI and InChIKey), bioactivity data (mainly inhibition of proteolytic enzymes), if applicable, and ID numbers from other biological and chemical databases. The database contains tools for determining the location of peptides in protein sequences (profiles of potential sensory activity), comparing protein sequences as precursors of sensory peptides based on the frequency of sensory fragments as a quantitative descriptor, simulating proteolysis and calculating novel parameters for quantitative description of simulated proteolysis. The BIOPEP database of sensory peptides and amino acids is available at http://www.uwm.edu.pl/biochemia/index.php/pl/biopep. It is an open access resource that does not require user registration.

Food protein-originating peptides as tastants - Physiological, technological, sensory, and bioinformatic approaches

Taste is one of the factors based on which the organism makes the selection of what to ingest. It also protects humans from ingesting toxic compounds and is one of the main attributes when thinking about food quality. Five basic taste sensations are recognized by humans: bitter, salty, sour, sweet, and umami. The taste of foods is affected by some molecules of some specific chemical nature. One of them are peptides derived from food proteins. Although they are not the major natural compounds originating from food sources that are responsible for the taste, they are in the area of scientific research due to the specific composition of amino acids which are well-known for their sensory properties. Literature data implicate that sweet, bitter, and umami are the tastes attributable to peptides. Moreover, the bitter peptide tastants are the dominant among the other tastes. Additionally, other biological activities like, e.g., inhibiting enzymes that regulate the body functions and acting as preventive food agents of civilization diseases, are also associated with the taste of peptides. The advance in information technologies has contributed to the elaboration of internet archives (databases) as well as in silico tools for the analysis of biological compounds. It also concerns peptides - namely taste carriers originating from foods. Thus, our paper provides a summary of knowledge about peptides as tastants with special attention paid to the following aspects: a) basis of taste perception, b) taste peptides detected in food protein sequences with special emphasis put on the role of bitter peptides, c) peptides that may enhance/suppress the taste of foods, d) databases as well as bioinformatic approaches suitable to study the taste of peptides, e) taste-taste interactions, f) basis of sensory analysis in the evaluation of the taste of molecules, including peptides, and g) the methodology applied to reduce/eliminate the undesired taste of peptides. The list of taste peptides serving some biological functions is presented in the Supplement file. The information provided includes database resources, whereas peptide sequences are given with InChiKeys, which is aimed at facilitating the Google® search. Our collection of data regarding taste peptides may be supportive for the scientists working with the set of peptide data in the context of structure-function activity of peptides.

Celiac Disease—Background, Molecular, Bioinformatics and Analytical Aspects

This review summarizes the background of celiac disease (CD), and the available bioinformatic and analytical methods designed to evaluate the molecular aspects of celiac-toxic proteins and peptides. CD is a T-cell-mediated autoimmune disease of the small intestine that is induced by ingestion of gluten proteins from wheat, barley, rye, and, rarely, after consumption of oats. This disease is characterized by malabsorption of nutrients from the intestine. It has been demonstrated that polypeptide chains of gliadin contain repeating amino acid sequences that constitute epitopes for a respective lymphocyte receptor (TCR). It was reported that the optimal length of a polypeptide chain suitable for a TCR is 10 to 15 amino acid residues. Celiac toxic proteins and peptides were characterized by the following methods and techniques: immunochemical, electrophoretic, chromatographic, and mass spectrometric. Characterization of celiac toxic peptides may provide sufficient information to breed out these sequences from wheat, barley or rye, whilst retaining its baking properties. An improved understanding of the immune response to gluten has provided an insight into possible future advances in the treatment of celiac disease.

Biological and Chemical Databases for Research into the Composition of Animal Source Foods

Bioinformatics and cheminformatics tools such as databases play an increasingly important role in modern science. They are commonly used in biological and medical sciences and they have many applications in food science. Databases listing biologically active compounds contribute to the design of functional foods and nutraceuticals. Databases of toxic or allergenic compounds are useful for food safety evaluations. This review presents examples of freely available databases (without obligatory registration) listing major groups of bioactive components. The main categories of compounds annotated in online databases include nucleic acids, proteins, peptides, carbohydrates, lipids, and low-molecular-weight compounds. Other categories of database entries are also discussed, including enzymes, allergens and their epitopes, flavor-enhancing compounds, as well as toxic substances. The last section of the review focuses on metabases, which are Web sites that create access to multiple databases.

Common Amino Acid Subsequences in a Universal Proteome--Relevance for Food Science.

A common subsequence is a fragment of the amino acid chain that occurs in more than one protein. Common subsequences may be an object of interest for food scientists as biologically active peptides, epitopes, and/or protein markers that are used in comparative proteomics. An individual bioactive fragment, in particular the shortest fragment containing two or three amino acid residues, may occur in many protein sequences. An individual linear epitope may also be present in multiple sequences of precursor proteins. Although recent recommendations for prediction of allergenicity and cross-reactivity include not only sequence identity, but also similarities in secondary and tertiary structures surrounding the common fragment, local sequence identity may be used to screen protein sequence databases for potential allergens in silico. The main weakness of the screening process is that it overlooks allergens and cross-reactivity cases without identical fragments corresponding to linear epitopes. A single peptide may also serve as a marker of a group of allergens that belong to the same family and, possibly, reveal cross-reactivity. This review article discusses the benefits for food scientists that follow from the common subsequences concept.