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1.
Immunomodulatory peptides-A promising source for novel functional food production and drug discovery.
Pavlicevic, M, Marmiroli, N, Maestri, E
Peptides. 2022;:170696
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Abstract
Immunomodulatory peptides are a complex class of bioactive peptides that encompasses substances with different mechanisms of action. Immunomodulatory peptides could also be used in vaccines as adjuvants which would be extremely desirable, especially in response to pandemics. Thus, immunomodulatory peptides in food of plant origin could be regarded both as valuable suplements of novel functional food preparation and/or as precursors or possible active ingredients for drugs design for treatment variety of conditions arising from impaired function of immune system. Given variety of mechanisms, different tests are required to assess effects of immunomodulatory peptides. Some of those effects show good correlation with in vivo results but others, less so. Certain plant peptides, such as defensins, show both immunomodulatory and antimicrobial effect, which makes them interesting candidates for preparation of functional food and feed, as well as templates for design of synthetic peptides.
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Ultrafast Fluorescence Spectroscopy via Upconversion and Its Applications in Biophysics.
Cao, S, Li, H, Zhao, Z, Zhang, S, Chen, J, Xu, J, Knutson, JR, Brand, L
Molecules (Basel, Switzerland). 2021;(1)
Abstract
In this review, the experimental set-up and functional characteristics of single-wavelength and broad-band femtosecond upconversion spectrophotofluorometers developed in our laboratory are described. We discuss applications of this technique to biophysical problems, such as ultrafast fluorescence quenching and solvation dynamics of tryptophan, peptides, proteins, reduced nicotinamide adenine dinucleotide (NADH), and nucleic acids. In the tryptophan dynamics field, especially for proteins, two types of solvation dynamics on different time scales have been well explored: ~1 ps for bulk water, and tens of picoseconds for "biological water", a term that combines effects of water and macromolecule dynamics. In addition, some proteins also show quasi-static self-quenching (QSSQ) phenomena. Interestingly, in our more recent work, we also find that similar mixtures of quenching and solvation dynamics occur for the metabolic cofactor NADH. In this review, we add a brief overview of the emerging development of fluorescent RNA aptamers and their potential application to live cell imaging, while noting how ultrafast measurement may speed their optimization.
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Mining the Biomarker Potential of the Urine Peptidome: From Amino Acids Properties to Proteases.
Trindade, F, Barros, AS, Silva, J, Vlahou, A, Falcão-Pires, I, Guedes, S, Vitorino, C, Ferreira, R, Leite-Moreira, A, Amado, F, et al
International journal of molecular sciences. 2021;(11)
Abstract
Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.
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Probiotics-Derived Peptides and Their Immunomodulatory Molecules Can Play a Preventive Role Against Viral Diseases Including COVID-19.
Manna, S, Chowdhury, T, Chakraborty, R, Mandal, SM
Probiotics and antimicrobial proteins. 2021;(3):611-623
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Abstract
As of recent, the pandemic episode of COVID-19, a severe acute respiratory syndrome brought about by a novel coronavirus (SARS-CoV-2) expanding the pace of mortality, has affected the disease rate profoundly. Invulnerability is the fundamental choice to prevent the ruining event of COVID-19, as the drugs and antibodies are in the phase of preliminary clinical trials. Within this brief period, a few strains of SARS-CoV-2 have been recognized by the vaccine manufacturers, which could be an incorrect guess about the strain that will end up spreading. Since the circulating SARS-CoV-2 strains continue to mutate, immunizations, if at all works, might be for a restricted time. We have not put sufficient time in research to understand the immune responses that correlate with protection as this could help refine vaccines. Here, we have summed up the adequacy of the immunomodulatory component of probiotics for the prevention against viral infections. Furthermore, an in silico data have been provided in support of the "probiotics-derived lipopeptides" role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction. In the current situation, probiotic treatment alongside chemotherapy may assist in bringing about substantial improvement of the health of COVID-19 patients. At the same time, probiotics may aid towards building up the immune defenses in people to evade COVID-19.
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Apolipoprotein Mimetic Peptides: Potential New Therapies for Cardiovascular Diseases.
Wolska, A, Reimund, M, Sviridov, DO, Amar, MJ, Remaley, AT
Cells. 2021;(3)
Abstract
Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.
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Potential Relevance of Bioactive Peptides in Sports Nutrition.
König, D, Kohl, J, Jerger, S, Centner, C
Nutrients. 2021;(11)
Abstract
Bioactive peptides are physiologically active peptides mostly derived from proteins following gastrointestinal digestion, fermentation or hydrolysis by proteolytic enzymes. It has been shown that bioactive peptides can be resorbed in their intact form and have repeatedly been shown to have a positive effect on health-related parameters such as hypertension, dyslipoproteinemia, inflammation and oxidative stress. In recent years, there has been increasing evidence that biologically active peptides could also play an important role in sports nutrition. Current studies have shown that bioactive peptides could have a positive impact on changes in body composition and muscular performance, reduce muscle damage following exercise and induce beneficial adaptions within the connective tissue. In the following overview, potential mechanisms as well as possible limitations regarding the sports-related effect of bioactive peptides and their potential mechanisms are presented and discussed. In addition, practical applications will be discussed on how bioactive peptides can be integrated into a nutritional approach in sports to enhance athletic performance as well as prevent injuries and improve the rehabilitation process.
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Late-Stage Diversification of Tryptophan-Derived Biomolecules.
Gruß, H, Sewald, N
Chemistry (Weinheim an der Bergstrasse, Germany). 2020;(24):5328-5340
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Abstract
Pd-mediated reactions have emerged as a powerful tool for the site-selective and bioorthogonal late-stage diversification of amino acids, peptides and related compounds. Indole moieties of tryptophan derivatives are susceptible to C2 H-activation, whereas halogenated aromatic amino acids such as halophenylalanines or halotryptophans provide a broad spectrum of different functionalisations. The compatibility of transition-metal-catalysed cross-couplings with functional groups in peptides, other biologically active compounds and even proteins has been demonstrated. This Review primarily compiles the application of different cross-coupling reactions to modify halotryptophans, halotryptophan containing peptides or halogenated, biologically active compounds derived from tryptophan. Modern approaches use regio- and stereoselective biocatalytic strategies to generate halotryptophans and derivatives on a preparative scale. The combination of bio- and chemocatalysis in cascade reactions is given by the biocompatibility and bioorthogonality of Pd-mediated reactions.
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Use of Non-Pharmacological Supplementations in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: A Critical Review.
Rosi, E, Grazioli, S, Villa, FM, Mauri, M, Gazzola, E, Pozzi, M, Molteni, M, Nobile, M
Nutrients. 2020;(6)
Abstract
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, with environmental and biological causal influences. Pharmacological medication is the first choice in ADHD treatment; recently, many studies have concentrated on dietary supplementation approaches to address nutritional deficiencies, to which part of non-responses to medications have been imputed. This review aims to evaluate the efficacy of non-pharmacological supplementations in children or adolescents with ADHD. We reviewed 42 randomized controlled trials comprised of the following supplementation categories: polyunsaturated fatty acids (PUFAs), peptides and amino acids derivatives, single micronutrients, micronutrients mix, plant extracts and herbal supplementations, and probiotics. The reviewed studies applied heterogeneous methodologies, thus making it arduous to depict a systematic overview. No clear effect on single cognitive, affective, or behavioral domain was found for any supplementation category. Studies on PUFAs and micronutrients found symptomatology improvements. Peptides and amino acids derivatives, plant extracts, herbal supplementation, and probiotics represent innovative research fields and preliminary results may be promising. In conclusion, such findings, if confirmed through future research, should represent evidence for the efficacy of dietary supplementation as a support to standard pharmacological and psychological therapies in children and adolescents with ADHD.
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Mechanisms of Disulfide Bond Formation in Nascent Polypeptides Entering the Secretory Pathway.
Robinson, PJ, Bulleid, NJ
Cells. 2020;(9)
Abstract
Disulphide bonds are an abundant feature of proteins across all domains of life that are important for structure, stability, and function. In eukaryotic cells, a major site of disulphide bond formation is the endoplasmic reticulum (ER). How cysteines correctly pair during polypeptide folding to form the native disulphide bond pattern is a complex problem that is not fully understood. In this paper, the evidence for different folding mechanisms involved in ER-localised disulphide bond formation is reviewed with emphasis on events that occur during ER entry. Disulphide formation in nascent polypeptides is discussed with focus on (i) its mechanistic relationship with conformational folding, (ii) evidence for its occurrence at the co-translational stage during ER entry, and (iii) the role of protein disulphide isomerase (PDI) family members. This review highlights the complex array of cellular processes that influence disulphide bond formation and identifies key questions that need to be addressed to further understand this fundamental process.
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The role of peptides cleaved from protein precursors in eliciting plant stress reactions.
Chen, YL, Fan, KT, Hung, SC, Chen, YR
The New phytologist. 2020;(6):2267-2282
Abstract
As sessile organisms, plants are exposed to diverse abiotic and biotic stresses, and thus have developed complex signaling mechanisms that orchestrate multiple stress responses. Plant peptides have recently emerged as key signaling molecules of stress responses, not only to mechanical wounding and pathogen infection but also to nutrient imbalance, drought and high salinity. The currently identified stress-related signaling peptides in plants are derived from proteolytic processing of protein precursors. Here, we review these protein-derived peptides and the evidence for their functions in stress signaling. We recommend potential research directions that could clarify their roles in stress biology, and propose possible crosstalk with regard to the physiological outcome. The stress-centric perspective allows us to highlight the crucial roles of peptides in regulating the dynamics of stress physiology. Inspired by historic and recent findings, we review how peptides initiate complex molecular interactions to coordinate biotic and abiotic stress responses in plants.