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Scientific Reports Aug 2016Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas' disease....
Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas' disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage. Using a combination of label-free and stable isotope labelling of cells in culture (SILAC) based proteomic strategies in the presence and absence of the NMT inhibitor DDD85646, we identified 56 proteins enriched in at least two out of the three experimental approaches. Of these, 6 were likely to be false positives, with the remaining 50 commencing with amino acids MG at the N-terminus in one or more of the T. cruzi genomes. Most of these are proteins of unknown function (32), with the remainder (18) implicated in a diverse range of critical cellular and metabolic functions such as intracellular transport, cell signalling and protein turnover. In summary, we have established that 0.43-0.46% of the proteome is N-myristoylated in T. cruzi approaching that of other eukaryotic organisms (0.5-1.7%).
Topics: Myristic Acid; Protein Processing, Post-Translational; Proteome; Protozoan Proteins; Trypanosoma cruzi
PubMed: 27492267
DOI: 10.1038/srep31078 -
Materials (Basel, Switzerland) Aug 2023This study aimed to address the issue of high-temperature challenges in asphalt pavement by developing two types of phase change materials (PCMs) for temperature...
This study aimed to address the issue of high-temperature challenges in asphalt pavement by developing two types of phase change materials (PCMs) for temperature control. Encapsulated paraffin wax particles (EPWP) and encapsulated myristic acid particles (EMAP) were synthesized using acid-etched ceramsite (AECS) as the carrier, paraffin wax (PW) or myristic acid (MA) as the core material, and a combination of epoxy resin and cement as the encapsulation material. The investigation encompassed leakage tests on PCMs; rutting plate rolling forming tests; SEM, FTIR, XRD, and TG-DSC microscopic tests; as well as heat storage and release tests and temperature control assessments using a light heating device. The study revealed the following key findings. Both types of PCMs exhibited no PCM leakage even under high temperatures and demonstrated low crushing ratios during rut-forming tests. Microscopic evaluations confirmed the chemical stability and phase compatibility of the constituents within the two types of PCMs. Notably, the phase change enthalpies of EPWP and EMAP were relatively high, measuring 133.31 J/g and 138.52 J/g, respectively. The utilization of AECS as the carrier for PCMs led to a substantial 4.61-fold increase in the adsorption rate. Moreover, the PCMs showcased minimal mass loss at 180 °C, rendering them suitable for asphalt pavement applications. The heat storage and release experiments further underscored the PCMs' capacity to regulate ambient temperatures through heat absorption and release. When subjected to light heating, the maximum temperatures of the two types of phase change Marshall specimens were notably lower by 6.6 °C and 4.8 °C, respectively, compared to standard Marshall specimens. Based on comprehensive testing, EPWP displayed enhanced adaptability and demonstrated substantial potential for practical implementation in asphalt pavements.
PubMed: 37687694
DOI: 10.3390/ma16176002 -
Physical Chemistry Chemical Physics :... Feb 2022A new toluidine blue-myristic acid photosensitizer derivate (TBOMyr) was investigated as a design molecule to bind simultaneously to cucurbit[7]uril (CB[7]) and human...
Binding of toluidine blue-myristic acid derivative to cucurbit[7]uril and human serum albumin: computational and biophysical insights towards a biosupramolecular assembly.
A new toluidine blue-myristic acid photosensitizer derivate (TBOMyr) was investigated as a design molecule to bind simultaneously to cucurbit[7]uril (CB[7]) and human serum albumin (HSA) with the aim of constructing a biosupramolecular assembly. Molecular docking and dynamics calculations revealed the main supramolecular and bio-molecular interactions of TBOMyr with the macrocycle or the protein, respectively. The addition of the negatively charged myristic acid-like tail resulted in a unique conformation of the CB[7] complex where the phenothiazine core was included in the cavity of CB[7], leaving the fatty acid portion free to interact with the protein. A favorable ternary interaction between TBOMyr, CB[7] and HSA was suggested by the calculations, and an experimental binding affinity in the order of 10 M was determined for the TBOMyr@CB[7] complex with HSA. The new TBOMyr derivative could find applications in photodynamic therapy benefiting from the biosupramolecular interactions as a transport system.
Topics: Bridged-Ring Compounds; Humans; Imidazoles; Molecular Docking Simulation; Myristic Acid; Serum Albumin, Human; Tolonium Chloride
PubMed: 35044390
DOI: 10.1039/d1cp04307b -
International Journal of Environmental... Jun 2021Ischemic stroke is a leading cause of motor impairment and psychosocial disability. Although free fatty acids (FFA) have been proven to affect the risk of stroke and...
Ischemic stroke is a leading cause of motor impairment and psychosocial disability. Although free fatty acids (FFA) have been proven to affect the risk of stroke and potentially dementia, the evidence of their impact on cognitive functions in stroke patients is lacking. We aimed to establish such potential relationships. Seventy-two ischemic stroke patients were prospectively analysed. Their cognitive functions were assessed seven days post-stroke and six months later as follow-up ( = 41). Seven days post-stroke analysis of serum FFAs levels showed direct correlations between Cognitive Verbal Learning Test (CVLT) and the following FFAs: C20:4n6 arachidonic acid and C20:5n3 eicosapentaenoic acid, while negative correlations were observed for C18:3n3 linolenic acid (ALA), C18:4 n3 stearidonic acid and C23:0 tricosanoic acid. Follow-up examination with CVLT revealed positive correlations with C15:0 pentadecanoid acid, C18:3n6 gamma linoleic acid, SDA, C23:0 tricosanoic acid and negative correlations with C14:0 myristic acid and C14:1 myristolenic acids. Several tests (Trail Making Test, Stroop Dots Trail, Digit Span Test and Verbal Fluency Test) were directly correlated mainly with C14:0 myristic acid and C14:1 myristolenic acid, while corresponding negatively with C18:1 vaccinic acid, C20:3n3 cis-11-eicosatrienoic acid, C22:1/C20:1 cis11- eicosanic acid and C20:2 cis-11-eicodienoic acid. No correlations between Montreal Cognitive Assessment (MOCA) test performed on seventh day, and FFAs levels were found. Saturated fatty acids play a negative role in long-term cognitive outcomes in stroke patients. The metabolic cascade of polyunsaturated fatty acids (n3 PUFA) and the synthesis of (AA) can be involved in pathogenesis of stroke-related cognitive impairment.
Topics: Cognition; Fatty Acids; Fatty Acids, Nonesterified; Humans; Stroke; Survivors
PubMed: 34208689
DOI: 10.3390/ijerph18126500 -
International Immunopharmacology Jun 2017Natural albumin ligand (fatty acids)-conjugated peptides can rapidly bind to circulating albumin and form complexes to control the release of peptides. The purpose of...
Natural albumin ligand (fatty acids)-conjugated peptides can rapidly bind to circulating albumin and form complexes to control the release of peptides. The purpose of this study was to prolong the half-life and immune-modulating effects of thymopentin (TP5) by using the albumin binding strategy. We synthesized myristic acid-modified TP5 (TP5-MA) by conjugating a myristic acid-acylated lysine to a permissive site of TP5, which improved the albumin binding affinity of TP5-MA and dramatically enhanced its stability in human plasma. We observed well-preserved bioactivities of TP5-MA in RAW264.7 macrophages using a tumor necrosis factor (TNF)-α stimulation assay. Moreover, the prolonged immune-modulating effect of TP5-MA was confirmed by the normalized CD4/CD8 ratio in immune-depressed rat models, which resulted in a reduced administration frequency (twice per week). In general, the enhanced pharmacokinetic and pharmacodynamic properties of TP5-MA make it a promising product for the treatment of immunodeficiency diseases.
Topics: Adjuvants, Immunologic; Animals; CD4-CD8 Ratio; Female; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunomodulation; Macrophages; Male; Mice; Mice, Inbred BALB C; Myristic Acid; Protein Binding; Protein Stability; RAW 264.7 Cells; Rats; Rats, Wistar; Serum Albumin; T-Lymphocytes; Thymopentin; Tumor Necrosis Factor-alpha
PubMed: 28365509
DOI: 10.1016/j.intimp.2017.03.025 -
Annual Review of Biochemistry Jun 2016Sirtuins are NAD(+)-dependent enzymes universally present in all organisms, where they play central roles in regulating numerous biological processes. Although early... (Review)
Review
Sirtuins are NAD(+)-dependent enzymes universally present in all organisms, where they play central roles in regulating numerous biological processes. Although early studies showed that sirtuins deacetylated lysines in a reaction that consumes NAD(+), more recent studies have revealed that these enzymes can remove a variety of acyl-lysine modifications. The specificities for varied acyl modifications may thus underlie the distinct roles of the different sirtuins within a given organism. This review summarizes the structure, chemistry, and substrate specificity of sirtuins with a focus on how different sirtuins recognize distinct substrates and thus carry out specific functions.
Topics: Acylation; Gene Expression; Histones; Humans; Hydrolysis; Kinetics; Lipoylation; Models, Molecular; Myristic Acid; NAD; Plasmodium falciparum; Protein Processing, Post-Translational; Protein Structure, Secondary; Sirtuins; Substrate Specificity; Succinic Acid; Thermotoga maritima
PubMed: 27088879
DOI: 10.1146/annurev-biochem-060815-014537 -
Journal of Food Science Jun 2022In this research, some physical and bioactive properties of tea samples collected from every processing stage of black tea production were investigated. The processing...
In this research, some physical and bioactive properties of tea samples collected from every processing stage of black tea production were investigated. The processing stages were significantly effective on the investigated properties (moisture content, color parameters [L , a , and b ], and pH values the total phenolic substance, antioxidant activity) (p < 0.01). The antioxidant activities were found to be at a high level in fresh tea but decreased during the processing stages. Furthermore, the lowest activity was observed in the drying stage for extracts prepared with water and in the drying and sorting stages for extracts prepared with ethanol. In addition, it was determined that palmitic acid, myristic acid, and capric acid as saturated fatty acids, oleic acid, heptadecenoic acid, and eicosenoic acid as unsaturated fatty acids formed the fatty acid profile. Palmitic acid was determined to be the dominant fatty acid in tea samples. PRACTICAL APPLICATION: Tea is a beverage known to have positive health effects. The chemical structure of tea is very effective in providing these positive effects on health. Black tea production takes place in five stages in general terms (withering, rolling, oxidation, drying, and sorting stages) after the harvesting. These processes are very effective in the quality properties of tea. This research provides information about effects of processing stages on black tea. Our results demonstrate that processing was significantly effective on the physicochemical and bioactive properties of tea. Functionality of bioactive compounds could be maintained by optimization of the applied processes.
Topics: Antioxidants; Camellia sinensis; Fatty Acids; Plant Extracts; Tea
PubMed: 35478099
DOI: 10.1111/1750-3841.16151 -
Molecules (Basel, Switzerland) May 2022New carriers of phytosterols; acylglycerols containing natural myristic acid at -1 and -3 positions and stigmasterol residue linked to -2 position by carbonate and...
New carriers of phytosterols; acylglycerols containing natural myristic acid at -1 and -3 positions and stigmasterol residue linked to -2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.
Topics: Calorimetry, Differential Scanning; Glycerides; Humans; Lipid Bilayers; Liposomes; Myristic Acid; Phytosterols; Stigmasterol
PubMed: 35684341
DOI: 10.3390/molecules27113406 -
Journal of the Science of Food and... Jul 2022The development of lipid-lowering products has become the focus of the food industry due to increasing consumer awareness of the relationship between diet and health....
BACKGROUND
The development of lipid-lowering products has become the focus of the food industry due to increasing consumer awareness of the relationship between diet and health. Recently, edible oleofoams have drawn attention due to their enormous potential in reformulating food products with reduced fat content and unique mouth feel.
RESULTS
We have developed an edible oleofoam system by whipping oleogel composed of fatty acid mixtures in sunflower oil. The crystal morphology, gelation properties, and foaming properties of these oleogels could be tailored by changing the ratio of stearic acid (SA) and myristic acid (MA). Specifically, SA/MA = 2:8 (2S8M) was demonstrated to have superior foaming capability and foam stability, likely due to the densely packed and uniformly distributed crystals formed at this fatty acid ratio. Small lipid crystals in 2S8M absorbed to the air-oil interface more efficiently, and together with the strengthened network established in the bulk phase, helped stabilize the foam structure. As a result, the 2S8M oleofoam showed excellent foaming properties: strong plasticity, significantly increased overrun (up to 63.56 ± 2.58%), and significantly improved foam stability. The X-ray diffraction (XRD) results indicated that the diffraction pattern observed for 2S8M samples at d-spacing of 4.20 and 3.79 Å was related to the characteristic peak of β' type crystals, which were responsible for the enhanced foaming capability of 2S8M oleogels. Oleophobic property of 2S8M increased, as indicated by wettability in oil phase, which could possibly drive crystals to the air-oil interface.
CONCLUSIONS
These results highlighted the importance of lipid crystal morphology in determining the whippability of oleogels. © 2021 Society of Chemical Industry.
Topics: Aerosols; Fatty Acids; Sunflower Oil; Temperature; X-Ray Diffraction
PubMed: 34841529
DOI: 10.1002/jsfa.11695 -
Chembiochem : a European Journal of... Jan 2019Protein myristoylation plays key roles in biological processes, for instance, in membrane attachment and activation of proteins and in mediating protein-protein and...
Protein myristoylation plays key roles in biological processes, for instance, in membrane attachment and activation of proteins and in mediating protein-protein and protein-lipid interactions. Furthermore, myristoylated proteins are involved in disorders, including cancer and viral infections. Therefore, new tools to study protein myristoylation are in high demand. Herein, we report the development of photoactivatable probes, based on a diazirine-substituted analogue of myristic acid. The probes bind to and, upon irradiation, covalently label the lipid-binding chaperone protein uncoordinated 119 (UNC119). UNC119 increases overall solubility and regulates specifically the transport of myristoylated proteins between intercellular membranes. The binding mode of the probes is similar to that of the myristate moiety, and the residues inside the hydrophobic pocket of UNC119 proteins that are critical for covalent binding have been identified. The interaction with UNC119 was also demonstrated in cell lysate by means of affinity enrichment. Moreover, it is shown that the myristate analogue can be incorporated into peptide substrates by N-myristoyl transferases of Leishmania and Trypanosoma protozoan parasites.
Topics: Acyltransferases; Adaptor Proteins, Signal Transducing; Fluorescent Dyes; Humans; Leishmania; Myristic Acid; Photochemical Processes; Trypanosoma
PubMed: 30129686
DOI: 10.1002/cbic.201800406