Specific Moieties Research Articles

Functional polymeric molecules for performing autonomous synthesis of particles with core-shell structures and customizable shapes.

Self-organization by the directed migration of components within a system is an important process in many applications, such as the unidirectional migration of motor proteins for transporting items to specific sites in a cell. This manuscript describes a class of functional polymeric molecules that have a set of instructions written by specific chemical moieties. These instructions allow the functional polymeric molecules to be used for autonomous synthesis of particles: particles with both functional core-shell structure and customizable shapes are fabricated for the first time. The functional polymeric molecules direct the large-scale migration of the liquid molecules to specific sites for forming the required customized structure of the particle, thus overcoming previous challenges of fabricating this class of particles. This first synthesis of this class of particles enables the development of novel applications: the concept of shape specificity for targeting sites. Both the basic structural properties (core-shell structure and customizable shape) are used in the specific applications of targeted drug delivery and imaging. The secure physical fit due to the complementary shapes enables the particles to remain locked in position for the targeting. Polymeric molecules are first shown to be highly capable of being encoded with instructions for autonomous synthesis of structured materials.

Mechanism of selective recognition of Lys48-linked polyubiquitin by macrocyclic peptide inhibitors of proteasomal degradation

Post-translational modification of proteins with polyubiquitin chains is a critical cellular signaling mechanism in eukaryotes with implications in various cellular states and processes. Unregulated ubiquitin-mediated protein degradation can be detrimental to cellular homeostasis, causing numerous diseases including cancers. Recently, macrocyclic peptides were developed that selectively target long Lysine-48-linked polyubiquitin chains (tetra-ubiquitin) to inhibit ubiquitin-proteasome system, leading to attenuation of tumor growth in vivo. However, structural determinants of the chain length and linkage selectivity by these cyclic peptides remained unclear. Here, we uncover the mechanism underlying cyclic peptide’s affinity and binding selectivity by combining X-ray crystallography, solution NMR, and biochemical studies. We found that the peptide engages three consecutive ubiquitins that form a ring around the peptide and determined requirements for preferential selection of a specific trimer moiety in longer polyubiquitin chains. The structural insights gained from this work will guide the development of next-generation cyclic peptides with enhanced anti-cancer activity.

QSAR Studies of Nitric Oxide Synthase Inhibitors

Background:: Nitric oxide is a free radical bioregulator controlling homeostasis, vasodilation, and inhibition of platelet aggregation, significantly implicated in the nervous and immune system functionality. In vivo it is produced by nitric oxide synthases (NOSs). Objective:: Overproduction of nitric oxide is linked to several inflammatory, immunological, and neurodegenerative diseases and for that, various compounds have been synthesized as inhibitors of NOSs. In this review, the QSAR analyses were summarized in a variety of compounds as potent inhibitors of NOSs, and the models derived through 1D, 2D and 3D QSAR analyses. Conclusion:: Ten groups of various NOS inhibitors and 17 1D, 2D, and 3D QSAR models and analyses were presented and discussed. A lack of hydrophobic terms was noticed in most of the cases. Chemical substituents were selected considering the increase either of the hydrophilicity and/or of hydrophobicity, bulkiness supported steric interactions, and point to potent inhibitors. CMR (Calculated Molar Refractivity) a steric variable, with a negative sign, underlines the critical effects participating on (in) an active site on the enzymes. Indicator variables imply the influence of specific structural moieties. Electronic parameters were found to be significant.

Development of fluorescent probes with specific recognition moiety for hydrogen polysulfide

Hydrogen polysulfide (H2Sn, n > 1) is an important component of reactive sulfur species (RSS), which is an important substance for maintaining the redox balance in cells. However, limited recognition moieties are available for hydrogen polysulfide probe design. In this study, we have constructed a small library containing several organic molecules to explore a new specific recognition moiety for H2Sn fluorescent probe design. To validate the discovery, two fluorescent probes, 7 and BCC, were further developed based on coumarin and its derivative. The probes exhibited desirable specificity for H2Sn monitoring, which can be used for detecting H2Sn in solution and cells. The new specific recognition moiety for H2Sn fluorescent probe design discovered in this work has certain guiding significance for development of H2Sn probes exploring biological roles in the future.

TACkling Cancer by Targeting Selective Protein Degradation.

Targeted protein degradation has emerged as an alternative therapy against cancer, offering several advantages over traditional inhibitors. The new degrader drugs provide different therapeutic strategies: they could cross the phospholipid bilayer membrane by the addition of specific moieties to extracellular proteins. On the other hand, they could efficiently improve the degradation process by the generation of a ternary complex structure of an E3 ligase. Herein, we review the current trends in the use of TAC-based technologies (TACnologies), such as PROteolysis TArgeting Chimeras (PROTAC), PHOtochemically TArgeting Chimeras (PHOTAC), CLIck-formed Proteolysis TArgeting Chimeras (CLIPTAC), AUtophagy TArgeting Chimeras (AUTAC), AuTophagosome TEthering Compounds (ATTEC), LYsosome-TArgeting Chimeras (LYTAC), and DeUBiquitinase TArgeting Chimeras (DUBTAC), in experimental development and their progress towards clinical applications.

Understanding the role of membrane cholesterol upon Epstein Barr virus infection in astroglial cells.

EBV infection has long been postulated to trigger multiple sclerosis (MS) and anti-EBV antibodies showed a consistent presence in MS patients. Previous reports from our group have shown that the EBV infects different brain cells. Entry of the virus in neuronal cells is assisted by several host factors including membrane cholesterol. By using an inhibitor, methyl-β-cyclodextrin (MβCD), we evaluated the role of membrane cholesterol in EBV infection and pathogenesis. The membrane cholesterol depleted cells were infected with EBV and its latent genes expression were assessed. Further, EBV-mediated downstream signalling molecules namely STAT3, RIP, NF-kB and TNF-α levels was checked at protein level along with spatial (periphery and nucleus) and temporal changes in biomolecular fingerprints with Raman microspectroscopy (RS). Upon treatment with MβCD, lmp1 and lmp2a suggested significant downregulation compared to EBV infection. Downstream molecules like STAT3 and RIP, exhibited a decrease in protein levels temporally upon exposure to MβCD while NF-kB levels were found to be increased. Further, the intensity of the Raman spectra exhibited an increase in triglycerides and fatty acids in the cytoplasm of EBV-infected LN-229 cells compared to MβCD+EBV. Likewise, the Raman peak width of cholesterol, lipid and fatty acids were found to be reduced in EBV-infected samples indicates elevation in the cholesterol specific moieties. In contrast, an opposite pattern was observed in the nucleus. Moreover, the ingenuity pathway analysis revealed protein molecules such as VLDLR, MBP and APP that are associated with altered profile of cholesterol, fatty acids and triglycerides with infection-related CNS disorders. Taken together, our results underline the important role of membrane cholesterol over EBV entry/pathogenesis in astroglia cells which further trigger/exacerbate virus-associated neuropathologies. These results likely to aid into the prognosis of neurological disease like MS.

Unveiling Alternative Oxidation Pathways and Antioxidant and Cardioprotective Potential of Amaranthin-Type Betacyanins from Spinach-like Atriplex hortensis var. 'Rubra'.

A comprehensive oxidation mechanism was investigated for amaranthin-type betacyanins with a specific glucuronosylglucosyl moiety isolated from Atriplex hortensis 'rubra' using liquid chromatography coupled to diode array detection and electrospray ionization tandem mass spectrometry (LC-DAD-ESI-MS/MS) and LC-Quadrupole-Orbitrap-MS (LC-Q-Orbitrap-MS). By employing one-dimensional (1D) and two-dimensional (2D) NMR, this study elucidates the chemical structures of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)-oxidized celosianins for the first time. These findings demonstrate alternative oxidation pathways for acylated betacyanins compared to well-known betanidin, betanin, and gomphrenin pigments. Contrary to previous research, we uncover the existence of 17-decarboxy-neo- and 2,17-bidecarboxy-xanneo-derivatives as the initial oxidation products without the expected 2-decarboxy-xan forms. These oxidized compounds demonstrated potent free radical scavenging properties. Celosianin (IC50 = 23 μg/mL) displayed slightly higher antioxidant activity compared to oxidized forms, 17-decarboxy-neocelosianin (IC50 = 34 μg/mL) and 2,17-bidecarboxy-xanneocelosianin (IC50 = 29 μg/mL). The oxidized compounds showed no cytotoxic effects on H9c2 rat cardiomyoblasts (0.1-100 μg/mL). Additionally, treatment of H9c2 cells with the oxidized compounds (0.1-10 μg/mL) elevated glutathione levels and exhibited protective effects against H2O2-induced cell death. These findings have significant implications for understanding the impact of oxidation processes on the structures and biological activities of acylated betalains, providing valuable insights for future studies of the bioavailability and biological mechanism of their action in vivo.

Finding structural requirements of structurally diverse α-glucosidase and α-amylase inhibitors through validated and predictive 2D-QSAR and 3D-QSAR analyses

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemic state. The α-glucosidase and α-amylase are considered two major targets for the management of Type 2 DM due to their ability of metabolizing carbohydrates into simpler sugars. In the current study, cheminformatics analyses were performed to develop validated and predictive models with a dataset of 187 α-glucosidase and α-amylase dual inhibitors. Separate linear, interpretable and statistically robust 2D-QSAR models were constructed with datasets containing the activities of α-glucosidase and α-amylase inhibitors with an aim to explain the crucial structural and physicochemical attributes responsible for higher activity towards these targets. Consequently, some descriptors of the models pointed out the importance of specific structural moieties responsible for the higher activities for these targets and on the other hand, properties such as ionization potential and mass of the compounds as well as number of hydrogen bond donors in molecules were found to be crucial in determining the binding potentials of the dataset compounds. Statistically significant 3D-QSAR models were developed with both α-glucosidase and α-amylase inhibition datapoints to estimate the importance of 3D electrostatic and steric fields for improved potentials towards these two targets. Molecular docking performed with selected compounds with homology model of α-glucosidase and X-ray crystal structure of α-amylase largely supported the interpretations obtained from the cheminformatic analyses. The current investigation should serve as important guidelines for the design of future α-glucosidase and α-amylase inhibitors. Besides, the current investigation is entirely performed by using non-commercial open-access tools to ensure easy accessibility and reproducibility of the investigation which may help researchers throughout the world to work more on drug design and discovery.

Recent Developments in the Detection of Organic Contaminants Using Molecularly Imprinted Polymers Combined with Various Analytical Techniques.

Molecularly imprinted polymers (MIPs) encompass a diverse array of polymeric matrices that exhibit the unique capacity to selectively identify a designated template molecule through specific chemical moieties. Thanks to their pivotal attributes, including exceptional selectivity, extended shelf stability, and other distinct characteristics, this class of compounds has garnered interest in the development of highly responsive sensor systems. As a result, the incorporation of MIPs in crafting distinctive sensors and analytical procedures tailored for specific analytes across various domains has increasingly become a common practice within contemporary analytical chemistry. Furthermore, the range of polymers amenable to MIP formulation significantly influences the potential utilization of both conventional and innovative analytical methodologies. This versatility expands the array of possibilities in which MIP-based sensing can be employed in recognition systems. The following review summarizes the notable progress achieved within the preceding seven-year period in employing MIP-based sensing techniques for analyte determination.

Atomically Dispersed Cobalt/Copper Dual-Metal Catalysts for Synergistically Boosting Hydrogen Generation from Formic Acid.

The development of practical materials for (de)hydrogenation reactions is a prerequisite for the launch of a sustainable hydrogen economy. Herein, we present the design and construction of an atomically dispersed dual-metal site Co/Cu-N-C catalyst allowing significantly improved dehydrogenation of formic acid, which is available from carbon dioxide and green hydrogen. The active catalyst centers consist of specific CoCuN6 moieties with double-N-bridged adjacent metal-N4 clusters decorated on a nitrogen-doped carbon support. At optimal conditions the dehydrogenation performance of the nanostructured material (mass activity 77.7 L ⋅ gmetal -1 ⋅ h-1 ) is up to 40 times higher compared to commercial 5 % Pd/C. In situ spectroscopic and kinetic isotope effect experiments indicate that Co/Cu-N-C promoted formic acid dehydrogenation follows the so-called formate pathway with the C-H dissociation of HCOO* as the rate-determining step. Theoretical calculations reveal that Cu in the CoCuN6 moiety synergistically contributes to the adsorption of intermediate HCOO* and raises the d-band center of Co to favor HCOO* activation and thereby lower the reaction energy barrier.

A Promising Approach: Magnetic Nanosystems for Alzheimer's Disease Theranostics.

Among central nervous system (CNS) disorders, Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and a major cause of dementia worldwide. The yet unclear etiology of AD and the high impenetrability of the blood-brain barrier (BBB) limit most therapeutic compounds from reaching the brain. Although many efforts have been made to effectively deliver drugs to the CNS, both invasive and noninvasive strategies employed often come with associated side effects. Nanotechnology-based approaches such as nanoparticles (NPs), which can act as multifunctional platforms in a single system, emerged as a potential solution for current AD theranostics. Among these, magnetic nanoparticles (MNPs) are an appealing strategy since they can act as contrast agents for magnetic resonance imaging (MRI) and as drug delivery systems. The nanocarrier functionalization with specific moieties, such as peptides, proteins, and antibodies, influences the particles' interaction with brain endothelial cell constituents, facilitating transport across the BBB and possibly increasing brain penetration. In this review, we introduce MNP-based systems, combining surface modifications with the particles' physical properties for molecular imaging, as a novel neuro-targeted strategy for AD theranostics. The main goal is to highlight the potential of multifunctional MNPs and their advances as a dual nanotechnological diagnosis and treatment platform for neurodegenerative disorders.

CREKA-modified liposomes target activated hepatic stellate cells to alleviate liver fibrosis by inhibiting collagen synthesis and angiogenesis.

Activated hepatic stellate cells (HSCs) are considered the key driver of excessive extracellular matrix and abnormal angiogenesis, which are the main pathological manifestations of hepatic fibrosis. However, the absence of specific targeting moieties has rendered the development of HSC-targeted drug delivery systems a significant obstacle in the treatment of liver fibrosis. Here we have identified a notable increase in fibronectin expression on HSCs, which positively correlates with the progression of hepatic fibrosis. Thus, we decorated PEGylated liposomes with CREKA, a peptide with high affinity for fibronectin, to facilitate the targeted delivery of sorafenib to activated HSCs. The CREKA-coupled liposomes exhibited enhanced cellular uptake in the human hepatic stellate cell line LX2 and selective accumulation in CCl4-induced fibrotic liver through the recognition of fibronectin. When loaded with sorafenib, the CREKA-modified liposomes effectively suppressed HSC activation and collagen accumulation in vitro. Furthermore. in vivo results demonstrated that the administration of sorafenib-loaded CREKA-liposomes at a low dose significantly mitigated CCl4-induced hepatic fibrosis, prevented inflammatory infiltration and reduced angiogenesis in mice. These findings suggest that CREKA-coupled liposomes have promising potential as a targeted delivery system for therapeutic agents to activated HSCs, thereby providing an efficient treatment option for hepatic fibrosis. STATEMENT OF SIGNIFICANCE: In liver fibrosis, activated hepatic stellate cells (aHSCs) are the key driver of extracellular matrix and abnormal angiogenesis. Our investigation has revealed a significant elevation in fibronectin expression on aHSCs, which is positively associated with the progression of hepatic fibrosis. Thus, we developed PEGylated liposomes decorated with CREKA, a molecule with a high affinity for fibronectin, to facilitate the targeted delivery of sorafenib to aHSCs.The CREKA-coupled liposomes can specifically target aHSCs both in vitro and in vivo. Loading sorafenib into CREKA-Lip significantly alleviated CCl4-induced liver fibrosis, angiogenesis and inflammation at low doses. These findings suggest that our drug delivery system holds promise as a viable therapeutic option for liver fibrosis with minimal risk of adverse effects.

Motif-Based Exploration of Halide Classes of Li5M10.5M20.5X8 Conductors Using the DFT Method: Toward High Li-Ion Conductivity and Improved Stability.

The development of all-solid-state lithium-ion batteries (ASSLIBs) is highly dependent on solid-state electrolyte (SSEs) performance. However, current SSEs cannot satisfactorily meet the requirements for high interfacial stability and Li-ion conductivity, especially under high-voltage cycling conditions. To overcome the intractable problems, we theoretically develop the chemistry of structural units to build a series of MX6-unit mixed framework Li5M10.5M20.5X8 (total 184 halides) for use as SSEs and recommend six halide candidates that combine the (electro)chemical stability with a low Li-ion migration barrier. Among them, three Li5M10.5M20.5F8 compounds (M1 = Ca and Mg; M2 = Ti and Zr) exhibit expansive electrochemical windows with a high cathodic limit (6.3 V vs μLi) and three-dimensional Li diffusion associated with moderate Li-migration barriers. To discuss their stability and compatibility (and in turn as a reference for experiments), the energy above the convex hull, the electrochemical stability window, the predicted (electro)reaction products, and the calculated reaction energies of Li5M10.5M20.5X8 in combination with Li-metal and several cathodes are tabulated. We stress that the importance of the cation-mixed effect and specific moieties for the halide anion leads to a design principle for a halide class of Li-ion SSEs. We provide insight into selecting the optimal halide anion and cations and open a new avenue of broad compositional spaces for stable Li-ion SSEs.

Cirsiliol and Quercetin Inhibit ATP Synthesis and Decrease the Energy Balance in Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Resistant Staphylococcus epidermidis (MRSE) Strains Isolated from Patients.

Polyphenols have attracted attention in the fight against antibiotic-resistant bacteria, as they show antibacterial action. Considering that polyphenols inhibit F1Fo-ATP synthase (ATP synthase) and that bacteria need a constant energy production to maintain their homeostasis, we evaluated the effect of two flavones, cirsiliol (tri-hy-droxy-6,7-dimethoxyflavone) and quercetin (3,3,4,5,7-pentahydroxyflavone), on energy production and intracellular ATP content in a methicillin-resistant Staphylococcus aureus (MRSA) strain and a methicillin-resistant Staphylococcus epidermidis (MRSE) strain isolated from patients, comparing the results to those obtained by treating the bacteria with oligomycin, a specific ATP synthase Fo moiety inhibitor. Real-time quantitative ATP synthesis and total ATP content of permeabilized Gram-positive bacteria were assayed by luminometry. The results showed that cirsiliol and quercetin inhibited ATP synthase and decreased the intracellular ATP levels in both strains, although the effect was higher in MRSE. In addition, while cirsiliol and quercetin acted immediately after the treatment, oligomycin inhibited ATP synthesis only after 30 min of incubation, suggesting that the different responses may depend on the different permeability of the bacterial wall to the three molecules. Thus, cirsiliol and quercetin could be considered potential additions to antibiotics due to their ability to target ATP synthase, against which bacteria cannot develop resistance.

On the O2 "Surfactant" Effect during Ag/SiO2 Magnetron Sputtering Deposition: The Point of View of In Situ and Real-Time Measurements.

The use of gaseous species has been proposed in the literature to counteract the three-dimensional growth tendency of noble metals on dielectric substrates and favor an earlier percolation without compromising electrical properties. This "surfactant" effect is rationalized herein in the case of O2 presence during magnetron sputtering deposition of Ag films on SiO2. In situ and real-time techniques (X-ray photoemission, film resistivity, UV-visible optical spectroscopy) and ex situ characterizations (X-ray diffraction and transmission electron microscopy) were combined to scrutinize the impact of O2 addition in the gas flow (%O2), revealing three regimes of evolution of film resistivity, morphology, structure, and chemical composition. At low oxygen flow conditions (%O2 < 4), the observed drastic decrease of the percolation threshold is assigned to a combination of (i) a change in nanoparticle density, wetting, and crystallographic texture and (ii) a delayed coalescence effect. The driving force is ascribed to the presence of specific adsorbed oxygen moieties, the nature of which starts evolving at intermediate oxygen flow conditions (10 ≤ %O2 < 20). At high oxygen flow (20 ≤ %O2 < 40), the found detrimental impact on film resistivity is assigned to an actual oxidation in the form of a Ag2O-like poorly crystallized compound. For all %O2, a composition gradient is observed across the film thickness, with a more metallic Ag at the substrate interface. A correlation between percolation and the nature of the detected O moieties is observed. In parallel to an oxygen spillover mechanism, this gradient can be explained by the competition between different surface processes occurring before percolation, namely, aggregation, metal oxidation, and substrate reactivity. Such findings pave the way to a rational use of O2 as a modifier for Ag growth.

Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G

Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV’s counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.

"Ghost" Fragment Ions in Structure and Site-Specific Glycoproteomics Analysis.

Mass spectrometry (MS) can unlock crucial insights into the intricate world of glycosylation analysis. Despite its immense potential, the qualitative and quantitative analysis of isobaric glycopeptide structures remains one of the most daunting hurdles in the field of glycoproteomics. The ability to distinguish between these complex glycan structures poses a significant challenge, hindering our ability to accurately measure and understand the role of glycoproteins in biological systems. A few recent publications described the use of collision energy (CE) modulation to improve structural elucidation, especially for qualitative purposes. Different linkages of glycan units usually demonstrate different stabilities under CID/HCD fragmentation conditions. Fragmentation of the glycan moiety produces low molecular weight ions (oxonium ions) that can serve as a structure-specific signature for specific glycan moieties; however, the specificity of these fragments has never been examined closely. Here, we particularly focused on N-glycoproteomics analysis and investigated fragmentation specificity using synthetic stable isotope-labeled N-glycopeptide standards. These standards were isotopically labeled at the reducing terminal GlcNAc, which allowed us to resolve fragments produced by the oligomannose core moiety and fragments generated from outer antennary structures. Our research identified the potential for false-positive structure assignments due to the occurrence of "Ghost" fragments resulting from single glyco unit rearrangement or mannose core fragmentation within the collision cell. To mitigate this issue, we have established a minimal intensity threshold for these fragments to prevent misidentification of structure-specific fragments in glycoproteomics analysis. Our findings provide a crucial step forward in the quest for more accurate and reliable glycoproteomics measurements.

Applications of autotrophic ammonia oxidizers in bio-geochemical cycles

Nitrogen is essential for life and to produce food. Still, nitrogen loss of the unused nitrogen in wastewater, air, freshwater, and oceans has caused nitrogen pollution, which impacts the environment and leads to eutrophication, climate change, biodiversity loss, and ozone depletion. It also causing cardio respiratory issues in humans. Anthropogenic activities such as food processing, fertilizer production, mining, and other impacting the global biogeochemical nitrogen cycle. Autotrophic ammonia-oxidizing microbial moieties such as ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and anaerobic ammonia-oxidizing bacteria (AnAOB) are being extensively used to remove nitrogen (present in the ammonia and ammonium forms). The conventional nitrogen removal process, “nitrification and denitrification,” has been highly used in wastewater treatment plants by employing a various bacterial communities. Since it required high organic compounds and an energy-intensive process, new strategies were being developed to reduce carbon footprint. “Anammox,” “Feammox,” and “Comammox” are a few processes that utilize specific bacterial moieties and do not require organic carbon. Among these, Anammox has become the most potential nitrogen removal system. In various studies, the combined Anammox and partial nitrification (PN/A) have shown the maximum nitrogen removal rate (NRR). This review discusses the applications of autotrophic ammonia oxidizers in agriculture, wastewater treatment plants, and engineered ecosystems. We have also addressed various stress impacts on ammonia oxidizers.

Which Moiety Drives Gangliosides to Form Nanodomains?

Gangliosides are important glycosphingolipids involved in a multitude of physiological functions. From a physicochemical standpoint, this is related to their ability to self-organize into nanoscopic domains, even at molar concentrations of one per 1000 lipid molecules. Despite recent experimental and theoretical efforts suggesting that a hydrogen bonding network is crucial for nanodomain stability, the specific ganglioside moiety decisive for the development of these nanodomains has not yet been identified. Here, we combine an experimental technique achieving nanometer resolution (Förster resonance energy transfer analyzed by Monte Carlo simulations) with atomistic molecular dynamic simulations to demonstrate that the sialic acid (Sia) residue(s) at the oligosaccharide headgroup dominates the hydrogen bonding network between gangliosides, driving the formation of nanodomains even in the absence of cholesterol or sphingomyelin. Consequently, the clustering pattern of asialoGM1, a Sia-depleted glycosphingolipid bearing three glyco moieties, is more similar to that of structurally distant sphingomyelin than that of the closely related gangliosides GM1 and GD1a with one and two Sia groups, respectively.

C7 reaction mechanism and its self-imitation in the kinetic modeling of PAH formation

Polycyclic aromatic hydrocarbons (PAHs), serving as critical soot precursors, are formed via complicated chemical processes, such as the first aromatic ring formation and the aromatic ring growth, from small molecules. Benzene/phenyl (“C6”) is commonly considered as the critical first aromatic ring formed, which has attracted many studies on its formation and its further mass growth. Reactions of cyclopentadienyl (“C5”) are also recognized as PAH formation pathways without involving benzene. Compared to “C5” and “C6”, less attention has been paid to “C7” aromatics, such as vinyl-cyclopentadienyl, tropyl and fulvenallenyl, for their roles in PAH formation. Previous PAH models included very few reactions of “C7” sub-mechanism, and somewhat ignored the self-consistency of the reaction networks of aromatic species with characteristic molecular structures. In this study, we upgraded “C7” sub-mechanism and revealed the self-imitation between the reaction network of monocyclic and polycyclic aromatic hydrocarbons. Model validation with literature experimental data shows that: a) benzyl, vinyl-cyclopentadienyl, tropyl, and fulvenallenyl are crucial intermediates in “C7” chemistry; b) “C7” resonance stabilized radicals (RSRs) are mainly contributed by different entrance channels from small aromatic precursors; c) the reactions of “C7” species provide unique contribution to PAH formation according to their specific molecular moieties. This study also reveals the basic aromatic classes, “C5”, “C6”, “C7”, and “fC7”, for the hierarchical reaction network, and the self-imitation between the hierarchical reaction networks of monocyclic and polycyclic aromatic hydrocarbons. Future work will build a kinetic model up to very large PAHs, close to soot nanoparticle, using the self-imitation of the hierarchical reaction network proposed in this study.