Functional Oligomers Research Articles

Polyethylene Glycol-Isophorone Diisocyanate Polyurethane Prepolymers Tailored Using MALDI MS.

The reaction of diols with isocyanates, leading to mono-functional and di-functional prepolymers may be investigated using various characterization methods which show the overall conversion of isocyanate monomers. On the other hand, matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) polymer characterization can be employed to identify the monomer units, the end-group functionalities, molecular weight averages, and to determine the copolymer sequence. Herein, we focus on prepolymer synthesis using isophorone diisocyanate (IPDI), a widely used diisocyanate for prepolymers preparation, especially in waterborne polyurethane materials. Thus, the reaction between polyethylene glycol diol and IPDI was in-depth investigated by mass spectrometry to determine the influence of the reaction parameters on the prepolymer's structure. The relative content of the different functional oligomer species at given reaction times was determined in the reaction mixture. More specifically, the offline analysis revealed the influence of reaction parameters such as reaction temperature, the concentration of reactants, and the amount of dibutyltin dilaurate catalyst. The established MALDI MS analysis involved measurements of samples, first, directly collected from the reaction mixture and secondly, following derivatization with methanol. The obtained results revealed the effects of reaction parameters on the functionalization reaction with isocyanates, allowing to achieve a better reaction control.

Polymers for the future

The main challenge of modern polymer science is to search for ways of further development of polymer civilization, which obviously includes living organisms on the Earth, without harmful consequences for civilization and the planet in its entirety. The review considers approaches to handle the problem of environmental accumulation of plastic waste. Promising trends in the development of polymer technologies, which can significantly reduce the amount of waste produced, are highlighted. Separate Sections address original methods of additive manufacturing technologies, such as the extrusion printing technique to produce multilayer films, 3D printing by using high-temperature polyimide materials, new functional siloxane oligomers and hydrogels for medical uses. Much attention is paid to the development and applications of biodegradable materials in medicine, packaging industry and agriculture. An analysis of the European strategy for plastics and plastic disposal demonstrates that it has a number of limitations due to high energy requirements and changes in Earth's carbon balance. The modern approach to plastic waste management free from these shortcomings is briefly outlined.<br> Bibliography — 1233 references.

Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family.

Oligomerization endows proteins with some key properties such as extra-stabilization, long-range allosteric regulation(s), and partnerships not accessible to their monomeric counterparts. How oligomerization is achieved and preserved during evolution is a subject of remarkable scientific relevance. By exploiting the abilities of the machine-learning algorithms implemented in AlphaFold (AF) in predicting protein structures, herein, we report a comprehensive analysis of the structural states of functional oligomers of all members of the KCTD protein family. Interestingly, our approach led to the identification of reliable three-dimensional models for the pentameric states of KCNRG, KCTD6, KCTD4, KCTD7, KCTD9, and KCTD14 and possibly for KCTD11 and KCTD21 that are involved in key biological processes and that were previously uncharacterized from a structural point of view. Although for most of these proteins, the CTD domains lack any sequence similarity, they share some important structural features, such as a propeller-like structure with a central cavity delimited by five exposed and regular β-strands. Moreover, the structure of the related proteins KCTD7 and KCTD14, although pentameric, appears to be characterized by a different organization of the CTD region, with the five chains forming a circle-like structure with a large cavity. Our predictions also suggest that other members of the family, such as KCTD10, KCTD13, and TNFAIP1, present a strong propensity to assume dimeric states. Although the structures of the functional oligomers reported herein represent models that require additional validations, they provide a consistent and global view of KCTD protein oligomerization.

Evaluation of the oligomeric epoxy silane as coupling agent on thermal and mechanical properties of water‐based acrylate adhesives

AbstractTo improve the thermal and mechanical properties of water‐based acrylate adhesives, epoxy functional silane oligomer (EFS) was investigated as a crosslinking agent at different curing temperatures from 100 to 140°C. Water‐based acrylate adhesives with different EFS concentrations (0.0–2.0 wt%) were prepared and characterized by Fourier transform infrared spectrometry (FT‐IR), colloidal stability, water absorption, mechanical and thermal properties. The thermal and mechanical properties of samples were investigated by means of differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), tensile testing, Izod impact, and dynamic mechanical analysis. The amount of EFS had a significant influence on the crosslinking process and curing temperature. FT‐IR and TGA analysis revealed successful crosslinking of EFS with the water‐based acrylate adhesive at 100°C temperature. The use of EFS after different curing processes showed higher tensile strength and lower water absorption. Among the percentage of EPS studied, the use of 1.0 wt% presented the most promising results for the improvement thermal and mechanical properties. In addition, the results obtained in this study provide new insights into the use of EFS as a coupling agent of water‐based acrylate adhesives for wood‐fiber composites, as well as in the particleboard panels industry.

Pharmacological induction of AMFR increases functional EAAT2 oligomer levels and reduces epileptic seizures in mice.

Dysregulation of excitatory amino acid transporter 2 (EAAT2) contributes to the development of temporal lobe epilepsy (TLE). Several strategies for increasing total EAAT2 levels have been proposed. However, the mechanism underlying the oligomeric assembly of EAAT2, impairment of which inhibits the formation of functional oligomers by EAAT2 monomers, is still poorly understood. In the present study, we identified E3 ubiquitin ligase AMFR as an EAAT2-interacting protein. AMFR specifically increased the level of EAAT2 oligomers rather than inducing protein degradation through K542-specific ubiquitination. By using tissues from humans with TLE and epilepsy model mice, we observed that AMFR and EAAT2 oligomer levels were simultaneously decreased in the hippocampus. Screening of 2386 FDA-approved drugs revealed that the most common analgesic/antipyretic medicine, acetaminophen (APAP), can induce AMFR transcriptional activation via transcription factor SP1. Administration of APAP protected against pentylenetetrazol-induced epileptogenesis. In mice with chronic epilepsy, APAP treatment partially reduced the occurrence of spontaneous seizures and greatly enhanced the antiepileptic effects of 17AAG, an Hsp90 inhibitor that upregulates total EAAT2 levels, when the 2 compounds were administered together. In summary, our studies reveal an essential role for AMFR in regulating the oligomeric state of EAAT2 and suggest that APAP can improve the efficacy of EAAT2-targeted antiepileptic treatments.

Spontaneous Formation of Functional Structures in Messy Environments.

Even though prebiotic chemistry initially deals with simple molecules, its composition rapidly gains complexity with oligomerization. Starting with, e.g., 20 monomers (such as the 20 proteinogenic amino acids), we expect 400 different dimers, 3,200,000 pentamers, or more than 1013 decamers. Hence, the starting conditions are very messy but also form a very powerful pool of potentially functional oligomers. A selecting structure (a “selector” such as membrane multilayers or vesicles) may pick and accumulate those molecules from the pool that fulfill a simple function (such as the suitability to integrate into a bilayer membrane). If this “selector” is, in turn, subject to a superimposed selection in a periodic process, the accumulated oligomers may be further trimmed to fulfill more complex functions, which improve the survival rate of the selectors. Successful oligomers will be passed from generation to generation and further improved in subsequent steps. After thousands of generations, the selector, together with its integrated oligomers, can form a functional unit of considerable order and complexity. The actual power of this process of random formation and selection has already been shown in laboratory experiments. In this concept paper, earlier results are summarized and brought into a new context.

Protein engineering and biochemical/biophysical approaches for structural studies of small membrane proteins and their complexes: Application to viroporins

We study the structure and function of small viral membrane proteins, which are expressed in the host and function in cellular membranes. Typically, they are multi‐domain multi‐functional proteins aiding virus adaptation and proliferation. Detailed characterization of the structure‐function relationship of these proteins will help to better understand virus‐host interactions and possibly develop protein inhibitors. However, such characterization is challenging due to the proteins’ small size and dynamic nature. Our focus is on viroporins, namely the Vpu, p7 and E proteins from HIV‐1, HCV, and CoV, respectively. Viroporins form ion‐conducting oligomers in cellular membranes leading to increased membrane permeability affecting ion homeostasis in infected cells. In addition, these proteins have soluble domains involved in interactions with host proteins. Currently, the structures of full‐length viroporins are largely uncharacterized and the information about the mechanism of oligomer formation and inter‐domain communication is very limited. Here, we report our effort to produce and solve the structure of stable viroporin oligomers in lipid environment. We use protein engineering to generate a range of fusion constructs aiming to increase the protein/oligomer size and reduce the conformational heterogeneity, thus making the protein amenable for structural determination by electron microscopy (EM) techniques. We produced, expressed in E. coli and purified, several soluble constructs of Vpu, p7 and E proteins fused at their N‐terminals to maltose binding protein (MBP). Thereafter, we interacted these proteins with lyso lipid mixtures of PC and PG, and their oligomerization was observed by negative staining EM and pulse electron paramagnetic resonance (EPR). We further use size‐exclusion chromatography (SEC) to assess the heterogeneity of viroporin oligomers in lyso PC/PG. Indeed, the protein elution exhibits a relatively broad chromatographic profile, indicating the presence of more than one oligomeric form. We further use SEC to test different protein‐to‐lipid molar ratios and the effect of viroporin inhibitor binding, aiming to shift the equilibrium toward stable functional viroporin oligomers. We will also discuss results from EM studies on these stable oligomers and EPR studies on spin‐labeled viroporin assembly. The progress we made in generating protein constructs and assessing protein oligomerization and stability in lipid provides a great promise for the development of successful methodology to determine the structure of full‐length viroporin. This methodology could also be applicable to other small oligomeric membrane proteins.

Bifunctional monomer oligomers-based composite molecularly imprinted membranes for the electrochemical monitoring of Sudan I.

Herein, we developed a highly sensitive electrochemical sensor for the trace detection of Sudan I (SDI) dye based on composite molecularly imprinted membranes (MIMs). The pentenyl (lipoic acyl)-isoleucyl-chitosan oligosaccharide (P(L)ICO) and pentenyl-asparaginyl-chitosan oligosaccharide (PASCO) served as bifunctional monomer oligomers. After deposition of gold nanoparticles on a glassy carbon electrode (GCE) surface, a P(L)ICO layer successfully self-assembled on the surface. Subsequently, the primary MIM was polymerised on the electrode surface by using SDI as a template, PASCO as a functional monomer oligomer, and ethylene glycol dimethacrylate as a cross-linking agent. Electrochemical polymerisation was then conducted in an N,N'-methylenebisacrylamide solution. After eluting the SDI molecules from the composite MIMs, the fabricated SDI-MIM(PM)/Fn-Au/GCE demonstrated specific adsorption of SDI. Under optimal conditions, the constructed sensor exhibited a linear relationship between decreasing peak current and SDI concentration from 0.02 to 3.5 μM with a low detection limit of 4 nM (S/N = 3). As a proof of concept, SDI-MIM(PM)/Fn-Au/GCE was also applied to detect SDI in chili powder samples, with recoveries ranging from 96.8 to 106.6%.

Self-healing epoxy coatings with microencapsulated ionic PDMS oligomers for corrosion protection based on supramolecular acid-base interactions

To obtain a self-healing coating and improve the corrosion resistance of coated low-carbon steel surfaces, a commercial epoxy coating was modified by adding microcapsules composed of a poly(methyl methacrylate) shell and a core of ionic polydimethylsiloxane (PDMS) oligomers. The encapsulation of amino- and carboxylic acid-terminated PDMS was achieved by a solvent evaporation process after the emulsification of core and shell materials, dissolved in CH2Cl2, in a suitable colloidal solution. A high core loading of nearly 50% wt. was successfully obtained by carefully increasing the interfacial tension of oil-in-water emulsion before the solvent evaporation. The microcapsule morphology was evaluated by SEM and optical microscopy analyses, which showed a particle diameter range of 20–70 μm. The presence of ionic PDMS oligomers as core materials was demonstrated by FTIR spectroscopy and thermogravimetric analysis (TGA), which was also employed to determine the core loading. The newly prepared microcapsules were then incorporated into the matrix of a commercial two-component epoxy coating. Corrosion protection abilities were assessed by comparing samples coated with a standard epoxy coating modified with a 20% wt. of microcapsules and the pristine epoxy coating. The corrosion protection performance of the modified coating was evaluated through electrochemical impedance spectroscopy (EIS) tests and potential vs time measurements, which showed that the microcapsules in the coating matrix caused a beneficial increase in barrier properties of a scratched coating. The surface damage triggered the release of functional PDMS oligomers, leading to the formation of a supramolecular ionic network and providing self-healing abilities to the modified coating.

Critical Domains in the Specific Binding of Radiolabeled Vip3Af Insecticidal Protein to Brush Border Membrane Vesicles from Spodoptera spp. and Cultured Insect Cells.

Vegetative insecticidal proteins (Vip3) from Bacillus thuringiensis have been used, in combination with Cry proteins, to better control insect pests and as a strategy to delay the evolution of resistance to Cry proteins in Bt crops (crops protected from insect attack by the expression of proteins from B. thuringiensis). In this study, we have set up the conditions to analyze the specific binding of 125I-Vip3Af to Spodoptera frugiperda and Spodoptera exigua brush border membrane vesicles (BBMV). Heterologous competition binding experiments revealed that Vip3Aa shares the same binding sites with Vip3Af, but Vip3Ca does not recognize all of them. As expected, Cry1Ac and Cry1F did not compete for Vip3Af binding sites. By trypsin treatment of selected alanine mutants, we were able to generate truncated versions of Vip3Af. Their use as competitors with 125I-Vip3Af indicated that only those molecules containing domains I to III (DI-III and DI-IV) were able to compete with the trypsin-activated Vip3Af protein for binding and that molecules only containing either domain IV or domains IV and V (DIV and DIV-V) were unable to compete with Vip3Af. These results were further confirmed with competition binding experiments using 125I-DI-III. In addition, the truncated protein 125I-DI-III also bound specifically to Sf21 cells. Cell viability assays showed that the truncated proteins DI-III and DI-IV were as toxic to Sf21 cells as the activated Vip3Af, suggesting that domains IV and V are not necessary for the toxicity to Sf21 cells, in contrast to their requirement in vivo.IMPORTANCE This study shows that Vip3Af binding sites are fully shared with Vip3Aa, only partially shared with Vip3Ca, and not shared with Cry1Ac and Cry1F in two Spodoptera spp. Truncated versions of Vip3Af revealed that only domains I to III were necessary for the specific binding, most likely because they can form the functional tetrameric oligomer and because domain III is supposed to contain the binding epitopes. In contrast to results obtained in vivo (bioassays against larvae), domains IV and V are not necessary for ex vivo toxicity to Sf21 cells.

Antibacterial and Fungicidal Activity of Guanidinium Oligomers

Guanidinium oligomers are a poorly studied class of organic compounds and attract attention due to their antimicrobial properties. Strengthening the antimicrobial properties and simplifying and reducing the cost of the synthesis of these compounds is promising for obtaining functional guanidine-containing oligomers with alkyl radicals of different lengths in their composition. The aim of this work is to study the bactericidal and fungicidal activities of newly synthesized oligomeric guanidinium bromides with alkyl radicals of various lengths. Methods. The synthesis of tetraalkyl-substituted guanidine-containing oligomers with an aromatic and aliphatic oligoether component was carried out by the reaction of guanidine-containing oligomers with terminal guanidine fragments and alkyl bromides (Alk=-C3H7, -C7H15, -C10H21) at a molar ratio (1:4) of components. Different types of microorganisms (clinical isolates, gram-positive and gramnegative bacteria, microscopic fungi) were used as test cultures to determine the biocidal activity of the obtained compounds. The bacteria were grown on meat-peptone agar for 48 hours, micromycetes – on beer wort agar (6°B) for 14 days. The hydrocarbon-oxidizing bacteria and micromycetes were incubated at a temperature of 28±2°C, and clinical bacterial isolates – at a temperature of 37±2°C. Antimicrobial activity of oligomers was determined by the standard disco-diffusion method, and fungicidal – by the method of wells in agar. Results. Tetraalkyl-substituted guanidinium bromide oligomers with various radicals (-C3H7, -C7H15, -C10H21) were obtained and their bactericidal and fungicidal activity against various groups of microorganisms was shown. It was found that the obtained oligomers at a concentration of 1–3% in aqueous solution inhibited the growth of gram-negative and gram-positive bacteria. Antimicrobial and fungicidal properties depended on the length of the alkyl radical, and as its length increased, the diameter of growth inhibition zones of bacteria and micromycetes were increased. For 3% solutions of tetraalkyl-substituted guanidine oligomer with aromatic oligoepoxide (Alk=-C10H21), the growth inhibition zones of bacteria were 18–21 mm. The bactericidal effect of oligomer based on aromatic oligoepoxide with alkyl radicals Alk=-C7H15, -C10H21 was 20–25% higher than that for variants with aliphatic oligoepoxide. All the tetraalkyl-substituted (Alk=-C7H15, -C10H21) guanidine-containing oligomers at a concentration of 1% solution showed fungicidal activity to almost all micromycetes, the growth inhibition zones for microscopic fungi on the 7th day were 7–20 mm. The largest growth inhibition zones of micromycetes (in the range 15–20 mm) were observed for oligomers with aromatic oligoepoxide and radicals Alk=-C10H21 and -C7H15 and aliphatic oligoepoxide with radical Alk=-C10H21 (in the range 15–20 mm). Conclusions. The length of the alkyl radical and the nature of the oligoether component affected the bactericidal and fungicidal properties of newly synthesized oligomers. With an increase of the length of the alkyl radical of guanidine-containing oligomers, their bactericidal and fungicidal properties increase, tetralkyl-containing oligomers are promising for use as disinfectants for indoor treatment and as additives in polymer compositions to protect them from bio-damage.

Covalent grafting of functional oligo-isoprenes onto silica-based surfaces to achieve robust elastomeric monolayers, thin films and coatings

A new methodology is presented to covalently graft polyisoprene from natural or recycled rubber on hydroxylated and silicon-containing surfaces. For this purpose, we first synthesized novel functional telechelic oligomers from natural rubber, bearing a hydroxyl group at one chain end and a silane group at the other, which allowed their direct tethering on silicon-based and other materials. As alternative approach, we also synthesized bi-functional telechelic oligomers with a ketone and an aldehyde end-moieties and they reacted selectively with surface amino groups, introduced via a pre-functionalization step using commercial amino-alkoxysilanes. A high glass surface coverage density was reached and the oligoisoprenes free chain-ends were converted to acrylate functions, to possibly grow more polymer or to engage a photopolymerization process with other bio-based acrylate-terminated telechelic oligoisoprenes, in order to obtain thick films. In this way, ultra-thin oligomer layers, copolymer brushes, as well as grafted films and bulk materials were formed and characterized at sub-nanometer resolution using X-rays Reflectivity. A strong covalent grafting of polyisoprene coatings was achieved and resisted to long immersions in water and aggressive organic solvents under strong mechanical agitation. The robust molecular, thin films, and bulk sheathings are versatile polymeric constituents and represent a new family of sustainable coatings.

GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain

Ca2+/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) is a key neuronal signaling protein and an emerging drug target. The central hub domain regulates the activity of CaMKIIα by organizing the holoenzyme complex into functional oligomers, yet pharmacological modulation of the hub domain has never been demonstrated. Here, using a combination of photoaffinity labeling and chemical proteomics, we show that compounds related to the natural substance γ-hydroxybutyrate (GHB) bind selectively to CaMKIIα. By means of a 2.2-Å x-ray crystal structure of ligand-bound CaMKIIα hub, we reveal the molecular details of the binding site deep within the hub. Furthermore, we show that binding of GHB and related analogs to this site promotes concentration-dependent increases in hub thermal stability believed to alter holoenzyme functionality. Selectively under states of pathological CaMKIIα activation, hub ligands provide a significant and sustained neuroprotection, which is both time and dose dependent. This is demonstrated in neurons exposed to excitotoxicity and in a mouse model of cerebral ischemia with the selective GHB analog, HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid). Together, our results indicate a hitherto unknown mechanism for neuroprotection by a highly specific and unforeseen interaction between the CaMKIIα hub domain and small molecule brain-penetrant GHB analogs. This establishes GHB analogs as powerful tools for investigating CaMKII neuropharmacology in general and as potential therapeutic compounds for cerebral ischemia in particular.

Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast.

Life requires the oligomerization of individual proteins into higher-order assemblies. In order to form functional oligomers, monomers must adopt appropriate 3D structures. Molecular chaperones transiently bind nascent or misfolded proteins to promote proper folding. Single missense mutations frequently cause disease by perturbing folding despite chaperone engagement. A misfolded mutant capable of oligomerizing with wild-type proteins can dominantly poison oligomer function. We previously found evidence that human-disease-linked mutations in Saccharomyces cerevisiae septin proteins slow folding and attract chaperones, resulting in a kinetic delay in oligomerization that prevents the mutant from interfering with wild-type function. Here, we build upon our septin studies to develop a new approach for identifying chaperone interactions in living cells, and use it to expand our understanding of chaperone involvement, kinetic folding delays, and oligomerization in the recessive behavior of tumor-derived mutants of the tumor suppressor p53. We find evidence of increased binding of several cytosolic chaperones to a recessive, misfolding-prone mutant, p53(V272M). Similar to our septin results, chaperone overexpression inhibits the function of p53(V272M) with minimal effect on the wild type. Unlike mutant septins, p53(V272M) is not kinetically delayed under conditions in which it is functional. Instead, it interacts with wild-type p53 but this interaction is temperature sensitive. At high temperatures or upon chaperone overexpression, p53(V272M) is excluded from the nucleus and cannot function or perturb wild-type function. Hsp90 inhibition liberates mutant p53 to enter the nucleus. These findings provide new insights into the effects of missense mutations.

Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes

ABSTRACT The community-associated Methicillin-resistant Staphylococcus aureus strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many S. aureus strains. In addition, δ-toxin exists in the S. aureus culture supernatant as both N-terminus formylated δ-toxin (fδ-toxin) and deformylated δ-toxin (dfδ-toxin) groups. Although δ-toxin has been studied for more than 70 years, its functions remain unclear. We isolated and purified PSMs from the supernatant of S. aureus MW2, and found fibrils and oligomers aggregates by Size Exclusion Chromatography. After analyzing PSM aggregates and using peptide simulations, we found that the difference in the monomer structure of fδ-toxin and dfδ-toxin might ultimately lead to differences in the aggregation ability: fδ-toxin and dfδ-toxin tend to form fibrils and oligomers respectively. Of note, we found that fδ-toxin fibrils enhanced the stability of biofilms, while dfδ-toxin oligomers promoted their dispersal. Additionally, oligomeric dfδ-toxin combined with PSMα to form a complex with enhanced functionality. Due to the different aggregation capabilities and functions of fδ-toxin and dfδ-toxin, we speculate that they may be involved in the regulation of physiological activities of S. aureus. Moreover, the dfδ-toxin oligomer not only provides a new form of complex in the study of PSMα, but also has significance as a reference in oligomer research pertaining to some human amyloid diseases.

Monte-Carlo Simulations of Soft Matter Using SIMONA: A Review of Recent Applications

Molecular simulations such as Molecular Dynamics (MD) and Monte Carlo (MC) have gained increasing importance in the explanation of various physicochemical and biochemical phenomena in soft matter and help elucidate processes that often cannot be understood by experimental techniques alone. While there is a large number of computational studies and developments in MD, MC simulations are less widely used, but they offer a powerful alternative approach to explore the potential energy surface of complex systems in a way that is not feasible for atomistic MD, which still remains fundamentally constrained by the femtosecond timestep, limiting investigations of many essential processes. This paper provides a review of the current developments of a MC based code, SIMONA, which is an efficient and versatile tool to perform large-scale conformational sampling of different kinds of (macro)molecules. We provide an overview of the approach, and an application to soft-matter problems, such as protocols for protein and polymer folding, physical vapor deposition of functional organic molecules and complex oligomer modeling. SIMONA offers solutions to different levels of programming expertise (basic, expert and developer level) through the usage of a designed Graphical Interface pre-processor, a convenient coding environment using XML and the development of new algorithms using Python/C++. We believe that the development of versatile codes which can be used in different fields, along with related protocols and data analysis, paves the way for wider use of MC methods. SIMONA is available for download under http://int.kit.edu/nanosim/simona.

Optimizing the performance of sustainable nail gel compositions using a mixture experimental design methodology

This study presents the development of two major classes of oligomers extensively used in nail gel formulations – urethane acrylates and polyester acrylates – using sustainable routes. To this end, a series of non-isocyanate acrylic functional polyurethane oligomers (NIPU-ACs) were synthesized by the reaction of cyclic carbonates with a stoichiometric excess of amine, followed by reacting the amine-end groups with methacrylic anhydride (MAAH) to introduce the acrylate functionalities. Moreover, a series of different bio-renewable based polyester oligomers (BR-PS) were synthesized from ring-opening esterification of epoxidized soybean oil (ESO) with various mono/di acids such as rosin, benzoic acid, and itaconic acid.Next, the mixture experimental design methodology was used to formulate two categories of sustainable nail gels based on NIPU-ACs and BR-PS oligomers. The formulations were then evaluated for a set of screening tests, and Design-Expert® software was used to determine the most suitable correlation between the variable parameters and responses. In each category, the optimized formulation was selected based on the desired performance criteria and evaluated for complementary tests. Finally, three-layer nail gels systems were also developed and tested for durability and removability.The nail gel systems developed in this study not only have eco-friendly composition but meet critical requirements such as fast-curing (1−2 min), easy removability (in 5 min), high gloss (> 85 T 60°), and high durability (> 10,000 wet scrub cycles, acetone double rubs > 100, and abrasion resistance of < 20 mg after 500 cycles). The combination of these attributes makes these nail gels attractive alternatives to the incumbent products for commercial markets.

Efficient incorporation of a polar comonomer for direct synthesis of hyperbranched polar functional ethylene oligomers

Hyperbranched polar functional ethylene oligomers with very high incorporation can be accessible via ethylene–MA co-oligomerization with iminopyridyl Pd(ii) catalysts.

Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly.

Accurate assembly of newly synthesized proteins into functional oligomers is crucial for cell activity. In this study, we investigated whether direct interaction of two nascent proteins, emerging from nearby ribosomes (co-co assembly), constitutes a general mechanism for oligomer formation. We used proteome-wide screening to detect nascent chain-connected ribosome pairs and identified hundreds of homomer subunits that co-co assemble in human cells. Interactions are mediated by five major domain classes, among which N-terminal coiled coils are the most prevalent. We were able to reconstitute co-co assembly of nuclear lamin in Escherichia coli, demonstrating that dimer formation is independent of dedicated assembly machineries. Co-co assembly may thus represent an efficient way to limit protein aggregation risks posed by diffusion-driven assembly routes and ensure isoform-specific homomer formation.

α-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones.

α-Crystallins are small heat-shock proteins that act as holdase chaperones. In humans, αA-crystallin is expressed only in the eye lens, while αB-crystallin is found in many tissues. α-Crystallins have a central domain flanked by flexible extensions and form dynamic, heterogeneous oligomers. Structural models show that both the C- and N-terminal extensions are important for controlling oligomerization through domain swapping. α-Crystallin prevents aggregation of damaged β- and γ-crystallins by binding to the client protein using a variety of binding modes. α-Crystallin chaperone activity can be compromised by mutation or posttranslational modifications, leading to protein aggregation and cataract. Because of their high solubility and their ability to form large, functional oligomers, α-crystallins are particularly amenable to structure determination by solid-state nuclear magnetic resonance (NMR) and solution NMR, as well as cryo-electron microscopy.