Arginine Derivatives Research Articles

Post-translational mutagenesis for installation of natural and unnatural amino acid side chains into recombinant proteins.

Methods for installing natural and unnatural amino acids and their modifications into proteins in a benign and precise manner are highly sought-after in protein science. Here we describe a protocol for 'post-translational mutagenesis' that enables the programmed installation of protein side chains through the use of rapid, mild and operationally simple free-radical chemistry performed on recombinantly expressed and purified proteins. By introduction of protein dehydroalanine (Dha) residues (in this instance, from a unique cysteine residue introduced by site-directed mutagenesis) as free-radical trapping 'tags' for downstream modification, exquisite control over the site of subsequent modification is achieved. Using readily available alkyl halide precursors and simple borohydride salts, alkyl radicals can be generated in aqueous solution. These alkyl radicals react rapidly with protein-bound Dha residues to yield functionalized protein products with new carbon-carbon bonds. Once the Dha is installed, the introduction of the desired functionality is limited only by the requirement for polarity matching of the generated radical with the Dha 'acceptor', the solubility of the alkyl halide precursors in aqueous solution and the kinetics of the reaction itself. For example, methylated derivatives of lysine, arginine and glutamine are readily accessible. Furthermore, as the side chains are constructed chemically, many unnatural modifications can also be directly introduced as part of the side chain, including isotope reporters (19F, 13C) that can be used in biophysical experiments such as protein NMR. From a suitable cysteine mutant of the target protein, the entire procedure for this chemical post-translational mutation takes 2 d and is readily performed by nonchemists.

Arginine derivatives of dicarboxylic acids from the parotid gland secretions of common toad Bufo bufo-New agonists of ionotropic γ-aminobutyric acid receptors.

Compounds activating γ-aminobutyric acid type A receptor were isolated from the toad Bufo bufo venom as a result of chromatographic separation. Analysis of the structure of these compounds by mass spectrometry and nuclear magnetic resonance showed that they are arginine derivatives of dicarboxylic acids and represent suberylarginine, pimeloylarginine, and adipoylarginine.

Surgical adhesive: Synthesis and properties of thermoresponsive Pluronic L‐31–3,4–dihydroxyphenylalanine–arginine derivatives

ABSTRACTA novel thermosensitive adhesive was synthesized by the esterification reaction of multihydroxyl Pluronic L‐31 with 3,4‐dihydroxy‐l‐phenylalanine and l‐arginine. Pluronic L‐31–DOPA–arginine derivative (PDA) gels, rapidly formed in situ with horseradish peroxidase and hydrogen peroxide, were used to explore the performance of efficient tissue adhesives. The results of their adhesive strength on porcine skin demonstrate that the structure of the polymers and temperature influenced the adhesiveness to tissue of the polymers. Compared with the PDAs at 25 °C, the PDAs at 37 °C showed superior adhesive strength. The attractive performance of the PDA gels were demonstrated by this study's results, which suggest biomedical applications in tissue‐adhesive devices in the future. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44729.

Improving selective targeting to macrophage subpopulations through modifying liposomes with arginine based materials.

The effects of surface modifications on liposomes using a library of arginine derivatives for improved drug delivery were examined. Both unmodified and modified liposomes were tested for their drug delivery properties and propensity for internalization by macrophages. All materials were characterized by dynamic light scattering (DLS) and zeta potential. The resulting liposomes were able to encapsulate doxorubicin with a loading efficiency greater than 90% and cumulative releases of less than 15% after 144 h. The internalization of these particles was examined by loading the liposomes with fluorescein or doxorubicin to test internalization through fluorescence level and half maximal inhibitory concentration (IC50), respectively. RAW 264.7 macrophages were activated with lipopolysaccharide (LPS) or interleukin-4 (IL-4) to induce M1- or M2-like phenotypes. Naïve macrophages were also studied. Most modified liposomes enhanced the cytotoxicity of doxorubicin compared to unmodified liposomes. Macrophage phenotype was also observed to influence the cytotoxicity of doxorubicin entrapped in modified liposomes, with some samples enhancing the cytotoxicity in LPS stimulated macrophages and some enhancing toxicity in IL-4 stimulated cells.

Synthesis, characterization and acute toxicity of new Schiff base derived from L-arginine and vanillin

Condensation of L-arginine with 4-hydroxy-3-methoxy benzaldehyde (vanillin) yielded a novel Schiff base derivative of arginine in good yield. This new Schiff base was characterized by elemental analysis, IR and 1 H NMR spectroscopy. The toxicity of the compound was also assayed via the determination of their LD 50 value by using Dixon method. Studied compound was found to have an LD 50 of 718.6 mg/kg of body weight.

Identifying Factors of Microparticles Modified with Arginine Derivatives That Induce Phenotypic Shifts in Macrophages.

Macrophages are key players in the progression of many diseases, ranging from rheumatoid arthritis to cancer. Drug delivery systems have the potential not only to transport payloads to diseased tissue but also to influence cell behavior. Here, poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) microparticles were modified with 14 different arginine derivatives. These particles were then incubated with interleukin-4 or lipopolysaccharide-stimulated macrophages or naïve macrophages (RAW 264.7). The phenotypic state of the macrophages was assessed by measuring arginase activity, tumor necrosis factor-α (TNF-α) secretion, and nitrite production. Partial least-squares analysis revealed material properties and descriptors that shifted the macrophage phenotype for the three cell conditions in this study. Material descriptors relating to secondary bonding were suggested to play a role in shifting phenotypes in all three macrophage culture conditions. These findings suggest that macrophage responses could be altered through drug delivery vehicles, and this method could be employed to assist in screening potential candidates.

Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation

Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain. In 3,310 individuals (mean age 58 ± 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, l-arginine, symmetric dimethylarginine (SDMA), and the ratio of l-arginine/ADMA to incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age- and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI 1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither l-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755-0.809). Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement.

Trimethyl-L‑lysine, the metabolic precursor of carnitine, and methylated derivatives of arginine in patients with cardiovascular diseases

Objective of the present study was to estimate the concentrations of methylated derivatives of L‑lysine and L‑arginine in patients with blood circulation disorders. Design and methods. We examined plasma samples of 151 patients with cardiovascular diseases, including 86 patients with aortic aneurysm and 47 with aortic stenosis, as well as normal subjects divided in two age groups. The concentrations of trimethyl-L‑lysine (TML), symmetric dimethyl-L‑arginine (SDMA) and asymmetric dimethyl-L‑arginine (ADMA) were determined by liquid chromatography after solid phase extraction. Results. Decreased TML level was found in all patients, regardless of diagnosis, but there was an increase in ADMA and SDMA concentrations in comparison to healthy individuals (p < 0,001). These changes were accompanied by an increase in the concentration of lactic acid. TML decline was lower in the subgroup of patients with aortic stenosis compared to the subgroup with aortic aneurysm (p < 0,05), and there was no difference in lactate/pyruvate ratio and homocysteine level compared to healthy people. No significant correlations between TML and ADMA, TML and SDMA were found. Conclusions. Patients with different cardiovascular disorders demonstrate an altered level of markers of mitochondrial and endothelial dysfunction. Determination of blood TML level allows monitoring of protein methylation in the body. Being a precursor of carnitine, TML may characterize the changes in fatty acids transport relating to mitochondrial dysfunction development.

New cationic vesicles prepared with double chain surfactants from arginine: Role of the hydrophobic group on the antimicrobial activity and cytotoxicity

Cationic double chain surfactants have attracted much interest because they can give rise to cationic vesicles that can be used in biomedical applications. Using a simple and economical synthetic approach, we have synthesized four double-chain surfactants with different alkyl chain lengths (LANHCx). The critical aggregation concentration of the double chain surfactants is at least one order of magnitude lower than the CMC of their corresponding single-chain LAM and the solutions prepared with the LANHCx contain stable cationic vesicles. Encouragingly, these new arginine derivatives show very low haemolytic activity and weaker cytotoxic effects than conventional dialkyl dimethyl ammonium surfactants. In addition, the surfactant with the shortest alkyl chain exhibits good antimicrobial activity against Gram-positive bacteria. The results show that a rational design applied to cationic double chain surfactants might serve as a promising strategy for the development of safe cationic vesicular systems.

L-Arginine Derivatives Are Associated with the Hyperthyroid State in the General Population.

Arginine (ARG) derivatives and thyroid function independently influence atherosclerotic processes. Since thyroid hormones may mediate the association between ARG derivatives and atherosclerosis, this study investigated whether asymmetric and symmetric dimethylarginines (ADMA and SDMA, respectively) as well as homoarginine (hARG) are associated with parameters of thyroid function in the general population. Cross-sectional data from 3689 individuals aged 20-81 years from the population-based Study of Health in Pomerania (SHIP-0) were analyzed. Thyroid function was defined according to serum concentrations of thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4). Low and high serum TSH were defined by the cutoffs 0.3 mIU/L and 3 mIU/L, respectively. Serum concentrations of ARG, ADMA, SDMA, and hARG were measured using liquid chromatography-tandem mass spectrometry. ARG, ADMA, SDMA, and hARG were associated with serum concentrations of TSH, fT3, and fT4 by median regression and with categorized TSH values by multinomial logistic regression adjusted for age, sex, smoking status, physical activity, body mass index, and estimated glomerular filtration rate. Levels of ADMA (relative risk [RR] = 5.40 [confidence interval (CI) 1.96-14.86]) and SDMA (RR = 3.55 [CI 1.01-12.70]) were associated with low TSH. In addition, ADMA (β = 0.38 [CI 0.23-0.45]) was positively associated with fT3, while both ADMA (β = 0.98 [CI 0.43-1.54]) and SDMA (β = 1.19 [CI 0.50-1.88]) were positively associated with fT4. No consistent associations of ARG and hARG with thyroid function were detected. The positive associations of ADMA and SDMA with low TSH, fT3, and fT4 argue for a relationship of arginine derivatives with increased thyroid function. This suggests that the atherogenic properties of ADMA and SDMA may be partially mediated by thyroid function.

Synthesis of Deuterium‐Labelled 3‐Hydroxy‐L‐arginine: Comparative Studies on Different Protecting‐Group Strategies

AbstractThe β‐hydroxy‐α‐amino acid 3‐hydroxy‐L‐arginine is an important intermediate in biosynthetic pathways involving 2‐oxoglutarate (2‐OG) dependent FeII oxygenases. It also plays an essential role in post‐translational modifications of ribosomal proteins. For profound studies on arginine‐hydroxylating enzymes, synthetic reference compounds are of utmost importance. However, the synthesis of β‐hydroxy‐α‐amino acids is often not trivial. In particular, the preparation of a densely functionalized compound such as 3‐hydroxy‐L‐arginine poses a challenge in terms of a protecting‐group strategy. We have previously established a concise synthesis of 3‐hydroxy‐L‐arginine that is suitable for the preparation of both 3‐epimers of this β‐hydroxy‐α‐amino acid. However, we have since observed a remarkable isomerization reaction upon removal of the hydrogenolytically cleavable protecting groups, thus limiting the reliability of our previously described route. In this paper, we report a comparative study of protecting‐group strategies for this synthetic route, including a newly developed, more robust pathway to the target amino acid. The versatility of this improved route is demonstrated by the synthesis of the deuterium‐labelled derivatives (3R)‐ and (3S)‐3‐hydroxy‐[5‐2H]‐L‐arginine. These new isotope‐labelled arginine derivatives represent important tools for the elucidation of biosynthetic pathways, such as the formation of the arginine‐derived amino acid epicapreomycidine in the biosynthesis of muraymycin nucleoside antibiotics.

ADMA and arginine derivatives in relation to non-invasive vascular function in the general population

ObjectiveNitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population. Approach and resultsIn 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations were observed between all measured arginine derivatives and vascular function measures, except of l-arginine and FMD and SDMA and PAT ratio. In multivariate adjusted linear regression analyses we could show statistically significant relationships between arginine derivatives and vascular function measures, which were influenced by age, sex and body mass index (BMI). Thus, a negative relationship between ADMA and FMD in females who were normal (beta: −0.095, P < 0.001) to overweight (beta: −0.071, P < 0.001) and a negative association of SDMA and FMD for middle-aged females was seen. The relationship between ADMA and PAT was negative for males who were normal (beta: −0.089, P < 0.001) to overweight (beta: −0.051, P = 0.007) and positive for obese females (beta: 0.073, P = 0.021). ConclusionsWe showed small but significant correlations between ADMA and related arginine derivatives and non-invasive vascular function measures representative of different vascular regions. The associations were markedly influenced by age, sex and BMI. These findings support a complex interplay of arginine metabolism and vascular function.

L-Arginine Pathway in COPD Patients with Acute Exacerbation: A New Potential Biomarker

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains a major cause of mortality. Clinical criteria of AECOPD are subjective. Biomarkers for AECOPD may aid in the initiation of early treatment. Increased production of asymmetric and symmetric dimethylarginine (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD.Methods: L-arginine metabolites quantified by high-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects.Results: Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p < 0.001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p < 0.001, respectively). A cut-off value ≥0.57 for SDMA was an independent variable to confirm AECOPD in a regression model (OR: 1.632, p = 0.001). All markers were significantly higher in the sera of both patient groups compared to the controls (p < 0.05, respectively).Conclusions: COPD is associated with elevated L-arginine, ADMA and SDMA serum levels. In patients with AECOPD, production of ADMA and SDMA are more pronounced presumably due to more severe hypoxic insult. Methylated arginine derivatives in the sera may help early recognition of AECOPD.

Transcriptomic profile of aguR deletion mutant of Lactococcus lactis subsp. cremoris CECT 8666.

Lactococcus lactis subsp. cremoris CECT 8666 (formerly GE2-14) is a dairy strain that catabolizes agmatine (a decarboxylated derivative of arginine) into the biogenic amine putrescine by the agmatine deiminase (AGDI) pathway [1]. The AGDI cluster of L. lactis is composed by five genes aguR, aguB, aguD, aguA and aguC. The last four genes are responsible for the deamination of agmatine to putrescine and are co-transcribed as a single policistronic mRNA forming the catabolic operon aguBDAC[1]. aguR encodes a transmembrane protein that functions as a one-component signal transduction system that senses the agmatine concentration of the medium and accordingly regulates the transcription of aguBDAC[2], which is also transcriptionally regulated by carbon catabolic repression (CCR) via glucose, but not by other sugars such as lactose and galactose [1], [3]. Here we report the transcriptional profiling of the aguR gene deletion mutant (L. lactis subsp. cremoris CECT 8666 ∆aguR) [2] compared to the wild type strain, both grown in M17 medium with galactose as carbon source and supplemented with agmatine. The transcriptional profiling data of AguR-regulated genes were deposited in the Gene Expression Omnibus (GEO) database under accession no. GSE59514.

L-Arginine and SDMA Serum Concentrations Are Associated with Subclinical Atherosclerosis in the Study of Health in Pomerania (SHIP).

ObjectiveEven though ˪-arginine (ARG) derivatives can predict cardiovascular mortality, their role as atherosclerotic biomarkers is unclear. We tested the hypothesis if asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and the sum of both (DMA) are positively, while ARG and ARG/ADMA ratio are inversely associated with carotid intima-media thickness (cIMT) and atherosclerotic plaque in the carotid artery.Approach and ResultsCross-sectional data of 1999 subjects (age: 45–81 years; 48.2% ♀) from the population-based Study of Health in Pomerania (SHIP-0) was used. Analysis of variance and logistic regression models were calculated and all adjusted models were corrected for sex, age, smoking status, waist-to-hip ratio and estimated glomerular filtration rate. Increased cIMT (>75th age-sex specific percentile) was found in 517 subjects (25.7%), while atherosclerotic plaque was detected in 1413 subjects (70.4%). SDMA tertiles were significantly positively associated with larger cIMT among subjects with high SDMA levels [>66th: 0.82 (95%-CI 0.80; 0.85) mm]. High SDMA levels were related to a higher odds ratio (OR) of increased cIMT [OR 1.39 (95%-CI 1.08; 1.79)]. Furthermore, ARG was positively associated with atherosclerotic plaques [OR 1.41 (95%-CI 1.07; 1.85)]. No relation was found for ADMA and atherosclerosis.ConclusionsIn conclusion, the hypothesis of a positive association between SDMA with an increased cIMT was confirmed. Unexpectedly, ARG was positively related to atherosclerotic plaque. In view of these inconsistent findings, the impact of ARG derivatives as atherosclerotic biomarkers deserves further research.

Biocatalytic synthesis, antimicrobial properties and toxicity studies of arginine derivative surfactants.

Two novel arginine-based cationic surfactants were synthesized using as biocatalyst papain, an endopeptidase from Carica papaya latex, adsorbed onto polyamide. The classical substrate N (α)-benzoyl-arginine ethyl ester hydrochloride for the determination of cysteine and serine proteases activity was used as the arginine donor, whereas decyl- and dodecylamine were used as nucleophiles for the condensation reaction. Yields higher than 90 and 80% were achieved for the synthesis of N (α)-benzoyl-arginine decyl amide (Bz-Arg-NHC10) and N (α)-benzoyl-arginine dodecyl amide (Bz-Arg-NHC12), respectively. The purification process was developed in order to make it more sustainable, by using water and ethanol as the main separation solvents in a single cationic exchange chromatographic separation step. Bz-Arg-NHC10 and Bz-Arg-NHC12 proved antimicrobial activity against both Gram-positive and Gram-negative bacteria, revealing their potential use as effective disinfectants as they reduced 99% the initial bacterial population after only 1h of contact. The cytotoxic effect towards different cell types of both arginine derivatives was also measured. Bz-Arg-NHCn demonstrated lower haemolytic activity and were less eye-irritating than the commercial cationic surfactant cetrimide. A similar trend could also be observed when cytotoxicity was tested on hepatocytes and fibroblast cell lines: both arginine derivatives were less toxic than cetrimide. All these properties would make the two novel arginine compounds a promising alternative to commercial cationic surfactants, especially for their use as additives in topical formulations.

Computational docking simulations of a DNA-aptamer for argininamide and related ligands.

The binding properties of sequence-specific nucleic acids (aptamers) to low-molecular-weight ligands, macromolecules and even cells attract substantial scientific interest. These ligand-DNA complexes found different applications for sensing, nanomedicine, and DNA nanotechnology. Structural information on the aptamer-ligand complexes is, however, scarce, even though it would open-up the possibilities to design novel features in the complexes. In the present study we apply molecular docking simulations to probe the features of an experimentally documented L-argininamide aptamer complex. The docking simulations were performed using AutoDock 4.0 and YASARA Structure software, a well-suited program for following intermolecular interactions and structures of biomolecules, including DNA. We explored the binding features of a DNA aptamer to L-argininamide and to a series of arginine derivatives or arginine-like ligands. We find that the best docking results are obtained after an energy-minimization of the parent ligand-aptamer complexes. The calculated binding energies of all mono-substituted guanidine-containing ligands show a good correlation with the experimentally determined binding constants. The results provide valuable guidelines for the application of docking simulations for the prediction of aptamer-ligand structures, and for the design of novel features of ligand-aptamer complexes.

Structure of arginine overlayers at the aqueous gold interface: implications for nanoparticle assembly.

Adsorption of small biomolecules onto the surface of nanoparticles offers a novel route to generation of nanoparticle assemblies with predictable architectures. Previously, ligand-exchange experiments on citrate-capped gold nanoparticles with the amino acid arginine were reported to support linear nanoparticle assemblies. Here, we use a combination of atomistic modeling with experimental characterization to explore aspects of the assembly hypothesis for these systems. Using molecular simulation, we probe the structural and energetic characteristics of arginine overlayers on the Au(111) surface under aqueous conditions at both low- and high-coverage regimes. In the low-density regime, the arginines lie flat on the surface. At constant composition, these overlayers are found to be lower in energy than the densely packed films, although the latter case appears kinetically stable when arginine is adsorbed via the zwitterion group, exposing the charged guanidinium group to the solvent. Our findings suggest that zwitterion-zwitterion hydrogen bonding at the gold surface and minimization of the electrostatic repulsion between adjacent guanidinium groups play key roles in determining arginine overlayer stability at the aqueous gold interface. Ligand-exchange experiments of citrate-capped gold nanoparticles with arginine derivatives agmatine and N-methyl-l-arginine reveal that modification at the guanidinium group significantly diminishes the propensity for linear assembly of the nanoparticles.

Ovalbumin Modified with Pyrraline, a Maillard Reaction Product, shows Enhanced T-cell Immunogenicity

The Maillard reaction (also referred to as "glycation") takes place between reducing sugars and compounds with free amino groups during thermal processing of foods. In the final stage of the complex reaction cascade, the so-called advanced glycation end products (AGEs) are formed, including proteins with various glycation structures. It has been suggested that some AGEs could have immunostimulatory effects. Here, we aimed to identify specific glycation structure(s) that could influence the T-cell immunogenicity and potential allergenicity of food allergens, using ovalbumin (OVA, an egg white allergen) as a model allergen. OVA was specifically modified with representative glycation structures: N(ε)-carboxymethyl lysine (CM-OVA), N(ε)-carboxyethyl lysine (CE-OVA), pyrraline (Pyr-OVA), or methylglyoxal-derived arginine derivatives (MGO-OVA). As well as AGE-OVA, a crude glycation product in thermal incubation of OVA with glucose, only Pyr-OVA, and not other modified OVAs, was efficiently taken up by bone marrow-derived murine dendritic cells (BMDCs). The uptake of Pyr-OVA was reduced in scavenger receptor class A (SR-A)-deficient BMDCs, but not in cells treated with inhibitors of scavenger receptor class B, galectin-3, or blocking antibodies against CD36, suggesting that pyrraline binds to SR-A. Compared with other modified OVAs, Pyr-OVA induced higher activation of OVA-specific CD4(+) T-cells in co-culture with BMDCs. Furthermore, compared with native OVA, AGE-OVA and Pyr-OVA induced higher IgE production in mice. Pyrraline could induce better allergen uptake by DCs via association with SR-A and subsequently enhance CD4(+) T-cell activation and IgE production. Our findings help us to understand how Maillard reaction enhances the potential allergenicity of food allergens.

Integrated genomics and metabolomics in nephrology

Applying 'omics' approaches such as genome-wide association studies (GWAS) and metabolome analyses, genes and metabolites have been identified to be associated with renal pathophysiology. Meta-analyses of GWAS from large epidemiologic cohorts uncovered several novel loci linked with estimated glomerular filtration rate and chronic kidney disease (CKD). Sophisticated analytical technologies, including mass spectrometry and nuclear magnetic resonance spectroscopy, allow the analyses of up to 4000 targeted and non-targeted metabolites in plasma, serum and urine. Several uraemic toxins were found that were increased in CKD. Among them, arginine derivatives like asymmetric dimethylarginine or tryptophane metabolites have been identified as promising candidates to target mechanisms of kidney disease progression. This review aims to summarize recent findings in clinical kidney diseases research revealed by 'omics' approaches with a clear focus on recent genomics and metabolomics efforts.