Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.     

Modeling Alcohol Dehydrogenase Catalysis in Deep Eutectic Solvent/Water Mixtures

The use of oxidoreductases (EC1) in non-conventional reaction media has been increasingly explored. In particular, deep eutectic solvents (DESs) have emerged as a novel class of solvents. Herein, an in-depth study of bioreduction with an alcohol dehydrogenase (ADH) in the DES glyceline is presented. The activity and stability of ADH in mixtures of glyceline/water with varying water contents were measured. Furthermore, the thermodynamic water activity and viscosity of mixtures of glyceline/water have been determined. For a better understanding of the observations, molecular dynamics simulations were performed to quantify the molecular flexibility, hydration layer, and intraprotein hydrogen bonds of ADH. The behavior of the enzyme in DESs follows the classic dependence of water activity (a_W) in non-conventional media. At low a_W values (<0.2), ADH does not show any activity; at higher a_W values, the activity was still lower than that in pure water due to the high viscosities of the DES. These findings could be further explained by increased enzyme flexibility with increasing water content.     

Intersecting Xenobiology and Neometabolism To Bring Novel Chemistries to Life

The diversity of life relies on a handful of chemical elements (carbon, oxygen, hydrogen, nitrogen, sulfur and phosphorus) as part of essential building blocks; some other atoms are needed to a lesser extent, but most of the remaining elements are excluded from biology. This circumstance limits the scope of biochemical reactions in extant metabolism – yet it offers a phenomenal playground for synthetic biology. Xenobiology aims to bring novel bricks to life that could be exploited for (xeno)metabolite synthesis. In particular, the assembly of novel pathways engineered to handle nonbiological elements (neometabolism) will broaden chemical space beyond the reach of natural evolution. In this review, xeno-elements that could be blended into nature's biosynthetic portfolio are discussed together with their physicochemical properties and tools and strategies to incorporate them into biochemistry. We argue that current bioproduction methods can be revolutionized by bridging xenobiology and neometabolism for the synthesis of new-to-nature molecules, such as organohalides.     

Molecular Recognition in C-Type Lectins: The Cases of DC-SIGN,Langerin, MGL,and L-Sectin

Carbohydrates play a pivotal role in intercellular communication processes. In particular, glycan antigens are key for sustaining homeostasis, helping leukocytes to distinguish damaged tissues and invading pathogens from healthy tissues. From a structural perspective, this cross-talk is fairly complex, and multiple membrane proteins guide these recognition processes, including lectins and Toll-like receptors. Since the beginning of this century, lectins have become potential targets for therapeutics for controlling and/or avoiding the progression of pathologies derived from an incorrect immune outcome, including infectious processes, cancer, or autoimmune diseases. Therefore, a detailed knowledge of these receptors is mandatory for the development of specific treatments. In this review, we summarize the current knowledge about four key C-type lectins whose importance has been steadily growing in recent years, focusing in particular on how glycan recognition takes place at the molecular level, but also looking at recent progresses in the quest for therapeutics.     

Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product-Inspired Library

A systematic, diversity-oriented synthesis approach was employed to access a natural product-inspired flavonoid library with diverse chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated, and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. In addition, the diversity of chemical properties contributed to performance diversity, and the driving chemical property was dependent on the scaffold. These results highlight the importance of key chemical features that may inform the creation of small-molecule, performance-diverse libraries to improve the efficiency and success of high-throughput screening campaigns.     

In situ compatibilization of a polyethylene,polypropylene, and polystyrene ternary blend through Friedel–Crafts alkylation

The Friedel–Crafts alkylation reaction has been applied to reactively compatibilize a ternary blend of high-density polyethylene (HDPE), polypropylene (PP), and polystyrene (PS). The reactions were carried out in an internal mixer using varying catalyst concentrations. The resulting compatibilizer was quantified after Soxhlet extraction. In addition, p-substitution due to the grafting of alkyl groups onto the PS benzene ring was identified via nuclear magnetic resonance spectroscopy. The size of the PS domain in the reactive compositions is decreased by 80%. Moreover, the phase in which PS droplets were dispersed varied, that is, in the nonreactive blends they were found in the PP phase and in the reactive blends they shifted toward the HDPE phase. The effect of the compatibilizing agent was to improve the mechanical properties of the blend. Even with the lowest catalyst content, the properties of elongation-at-break, tensile strength, toughness, and elastic modulus showed improvements. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48295.     

Influence of carboxymethylation on the gelling capacity,rheological properties,and antioxidant activity of feruloylated arabinoxylans from different sources

Feruloylated arabinoxylans (FAX) are gelling polysaccharides presenting antioxidant activity (AC) and potential application as delivery systems. The influence of carboxymethylation on the gelling capacity, rheological properties, and AC of FAX from wheat flour (FAX1) and maize distillers grains (FAX2) was analyzed. The degree of substitution of carboxymethyl groups was 0.27 and 1.77 for carboxymethylated FAX1 (CFAX1) and FAX2 (CFAX2), which presented a change in M _n from 446 to 362 kDa and from 120 to 180 kDa, and a loss in FA content from 1.05 to traces and from 10.13 to 0.12, respectively, after carboxymethylation. G′ value at the end of rheological tests for FAX1 (71 Pa) and FAX2 (726 Pa) was higher than the corresponding G″ value. In contrast, G″ value for CFAX1 (0.35 Pa) and CFAX2 (0.03 Pa) was higher than the respective G′ value, indicating that they do no form gels. The AC increased in CFAX1 in relation to FAX1 from 4.49 to 8.30 mmol Trolox equivalent antioxidant capacity (TEAC) kg⁻¹, respectively, while it decreased in CFAX2 with regard to FAX2 from 11.31 to 9.43 mmol TEAC kg⁻¹, respectively. Carboxymethylation could be a path to design FAX derivatives offering alternative potential applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48325.     

Tuning the pH-responsiveness capability of poly(acrylic acid-co-itaconic acid)/NaOH hydrogel: Design,swelling, and rust removal evaluation

The swelling behavior of poly(acrylic acid-co-itaconic acid)/NaOH hydrogel as well as its ability for iron and copper rust removal was studied and established for the first time. Through an experimental design, the influence of the synthesis parameters on hydrogel response was determined. It was found that pH-responsiveness dependence of hydrogel determines its application. In alkaline media, the hydrogel acted as superabsorbent, while in acidic, the most outstanding property was its pickling capability that allowed to clean carbon steel and copper metallic surfaces. Infrared, thermogravimetry, and scanning electron microscopy were performed to determine copolymer formation, thermal properties, and morphology. Metallic crystallographic phases formed during the corrosion processes were determined by X-ray diffractometer. Hydrogel adhesiveness followed by diffusion and dissolution of metal oxides species was identified as the main steps in the rust removal mechanism. This method offers a new, environmentally friendly perspective to eliminate corrosion from metallic surfaces compared with traditional strategies. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48403.     

Effects of processing conditions on hybrid filler selective localization,rheological, and thermal properties of poly(ε-caprolactone)/poly(lactic acid) blends

In this study, the effects of processing conditions through different mixing sequences were used to analyze the factors, which could influence the hybrid filler selective localization in an immiscible polymer blend and how localization can influence the rheological and thermal properties. Different selective localizations were observed depending on the mixing sequence used when the hybrid filler was added. Notably, nanoparticles can interact with each other, which favor a synergy between them and alters, besides the localization, the dispersion state, or can interact with one polymer phase, and also alter the nanoparticles' selective localization. An improvement in rheological properties was observed in the hybrid nanocomposite in which there was interaction between the nanoparticles, favoring the hexagonal boron nitride exfoliation. On the other hand, for the storage modulus and degree of crystallinity, the sharpest increase occurred in the hybrid nanocomposite in which the nanoparticles could interact preferably with one polymer phase. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 137, 48711.