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Flexible and stretchable electrodes have been extensively explored in recent decades, promoting remarkable advances in wearable electronics. However, for the foreseeable future it will be hard to achieve a level of conductivity of stretchable electrodes equivalent to that of metallic electrodes, which undermines the potential for practical applications, especially for fiber-shaped electrodes with long length/diameter. Herein, the basic physical concept of the small resistance of parallel circuits was applied to a triboelectric nanogenerator (TENG) fiber/textile to dilute the negative effects of the huge resistance of stretchable electrode fibers. As a demonstration of the concept, stretchable gel electrode-based fibers were woven into parallel multi-fiber TENG structures (parallel-teng), which significantly reduced electrode resistance compared to single long-fiber knitting TENG (GS-teng). The output current of parallel-teng showed an 11.8 fold enhancement compared to that of GS-teng owing to the decrease in the inner resistance by an order of magnitude. This work demonstrates an easy method to reduce the electrode resistance using parallel multi-fiber structures, which provide an approach for dealing with low conductivity electrodes in practical application. Furthermore, other wearable devices where there is the challenge of stretchable high resistance of electrode fibers, such as fiber batteries and piezoelectric fibers, could be inspired by this work because of the versatility of the physical concept.

Improved understanding of the effect of protein glycosylation is expected to provide the foundation for the design of protein glycoengineering strategies. In this study, we examine the impact of O-glycosylation on the binding selectivity of a model Family 1 carbohydrate-binding module (CBM), which has been shown to be one of the primary sub-domains responsible for non-productive lignin binding in multi-modular cellulases. Specifically, we examine the relationship between glycan structure and the binding specificity of the CBM to cellulose and lignin substrates. We find that the glycosylation pattern of the CBM exhibits a strong influence on the binding affinity and the selectivity between both cellulose and lignin. In addition, the large set of binding data collected allows us to examine the relationship between binding affinity and the correlation in motion between pairs of glycosylation sites. Our results suggest that glycoforms displaying highly correlated motion in their glycosylation sites tend to bind cellulose with high affinity and lignin with low affinity. Taken together, this work helps lay the groundwork for future exploitation of glycoengineering as a tool to improve the performance of industrial enzymes., Improved understanding of the effect of protein glycosylation is expected to provide the foundation for the design of protein glycoengineering strategies.

Through full flexible realization of a new energy harvesting mode using only common fiber materials as active components by adopting a computerized knitting programme strategy, herein we developed a new kind of all-textile energy harvesters (A-TEHs) with a three-dimensional fabric structural integrity that can harvest and convert mechanical energy to electricity directly. The electric performance of obtained A-TEHs working at a single-electrode mode was extraordinary, which can generate a maximum power density of 1768.2 mW m−2 by 1200 N at a matched resistance load of 50 MΩ, and directly light up over 320 LEDs instantaneously by a single impact with an effective area of only 56.7 cm2. When A-TEH was used to charge a 200 µF commercial capacitor storage device with a bridge rectifier, its charging capacity increased with the triggering force, ranging from 6.7 mV s−1 at 100 N to 11.3 mV s−1 at 1400 N. Benefiting from the full structural integrity of fiber materials, A-TEHs, for the first time, truly realized the excellent textile properties that all wearable electronics try to achieve, including safety, lightweight, comfort, breathability, washability, and unique advantage of tailorability, leading to a kind of truly wearable energy harvesters with versatile product designability.

Natural proteins are an important source of therapeutic agents and industrial enzymes. While many of them have the potential to be used as highly effective medical treatments for a wide range of diseases or as catalysts for conversion of a range of molecules into important product types required by modern society, problems associated with poor biophysical and biological properties have limited their applications. Engineering proteins with reduced side-effects and/or improved biophysical and biological properties is therefore of great importance. As a common protein modification, glycosylation has the capacity to greatly influence these properties. Over the past three decades, research from many disciplines has established the importance of glycoengineering in overcoming the limitations of proteins. In this review, we will summarize the methods that have been used to glycoengineer proteins and briefly discuss some representative examples of these methods, with the goal of providing a general overview of this research area.

The conventional use of textiles as substrates for the incorporation of brick materials (i.e., polymers and nanomaterials) is ubiquitously developed with primary purposes for introducing desired technical/functional performance rather than maintaining the aesthetic/decorative characteristics and inherent advantages (i.e., flexibility and permeability) of textiles. Such kinds of modified textiles with typical solid coating layers, however, are becoming more and more unsuitable for some emerging applications, such as smart wearable devices. Herein, we presented a brand-new kind of modified textiles with brick materials formed contouring to the nonplanar fiber surfaces of a fabric substrate as a three-dimensional (3D) conformal layer of porous microstructures by a unique breath figure self-assembling strategy of employing water microdroplet arrays as soft dynamic templates that can be controlled, formed, and removed spontaneously. In this paper, the main influential factors such as solution concentration, relative humidity, temperature, brick materials, and fabric substrates were studied systematically to control and adjust the formation of 3D conformal porous microstructures (3CPMs). The obtained 3D conformal porous microstructured textiles (3CPMTs) hierarchically combining the inherent texture features of the porous network of textiles and honeycomb porous microstructures templated from water microdroplet arrays not only possess new functions of introduced brick materials (such as triboelectric performance and wettability) and maintain the excellent inherent advantages (such as flexibility, air permeability, water vapor permeability, and unique texture features) of fabrics but also enhance the tensile strength and thermal insulation performance of substrates. Taking advantage of the introduced functions, they can be either used for conventional applications (i.e., oil/water separation) with enhanced performance or explored for new applications (i.e., self-powered sensors with textile breathability and comfort) with truly wearable potential. We believe this efficient, robust, and versatile strategy opens up numerous possibilities for designing and developing a broad range of advanced multifunctional textiles upon end uses.

With rapid advancement in wearable electronics, textile-based triboelectric nanogenerators (T-TENGs) have attracted great attention for energy harvesting and bio-motion sensing because of their softness, lightweight, and comfort properties. However, the interface bonding between functional materials and textile substrate, and the compatibility with manufacturing still face considerable challenges. Herein, a kind of scalable core–spun coating yarn-based triboelectric nanogenerators (CSCY-TENGs) with a hierarchical architecture is designed and developed via continuous manufacturing which integrates yarn spinning, coating and braiding technologies to achieve fully continuous production. In this method, spinning technology was used to spin a kind of conductive core-spun yarns with silver-plated nylon yarn (SNY) as core and insulating cotton fibers as shell, where SNY serves as electrode and cotton fibers serve as base materials for absorbing/coating with triboelectric materials. Then multiple core-spun yarns coated with nylon and doped polydimethylsiloxane are used as positive and negative triboelectric materials to realize hierarchical CSCY-TENGs by braiding technology. The CSCY-TENGs can be washed and compatible with industrial-scale manufacturing. Besides, it can achieve an output voltage of 174 V, and a peak power density and an average power density of 275 mW/m2 and 57 mW/m2 respectively. As demonstration, the CSCY-TENG can charge various commercial capacitors and power low-power electronics. It can also be used as an anti-theft alarm carpet and energy harvesting shoes for bio-motion detection and energy harvesting.

The rapid advancement of flexible and stretchable electronics has attracted intensive attention in recent decades. However, challenges still remain in developing wearable and sustainable power sources with comparable portability and stretchability. Here, a novel type of stretchable fiber-shaped triboelectric nanogenerator (AXF-TENG) was fabricated by inserting a negative Poisson-ratio auxetic fiber into a positive Poisson-ratio hollow circular sleeve, forming a synergistic structured TENG composed of opposite Poisson's ratios. Owing to the advanced structural designs, the inner auxetic fiber would expand in all directions to more effectively contact with the shrunk outer steel wire sleeve under stretching. The peak-to-peak voltage and transfer charge of composite based AXF-TENG could reach up to 42 V and 12.5 nC, respectively. The fabricated AXF-TENG can be used as a self‐powered multifunctional sensor to detect human motions and be woven into an energy‐harvesting fabric to scavenge biomechanical energy. With open-circuit voltage of 46 V and maximum instantaneous power density of 52.36 mW/m2, the AXF-TENG fabric was capable of lighting up 20 light emitting diodes (LEDs), charging commercial capacitors, powering an electronic watch and a calculator. All of these merits of the proposed AXF-TENGs suggest their promising potentials for versatile applications in biomechanical energy harvesting and self-powered sensing.

Protein glycosylation is a diverse post-translational modification that serves myriad biological functions. O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions. However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs). Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker. Upon exposure to thermolysin, O-mannosylation, by far, provides the highest extent of proteolysis protection. To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan–peptide bond strongly influences the conformational features of the linker. Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan–protein backbone orientation. We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein–glycan interactions, protein flexibility, and protein stability. Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.

Many human proteins have the potential to be developed as therapeutic agents. However, side effects caused by direct administration of natural proteins have significantly slowed expansion of protein therapeutics into the clinic. Post-translational modifications (PTMs) can improve protein properties, but because of significant knowledge gaps, we are considerably limited in our ability to apply PTMs to generate better protein therapeutics. Here, we seek to fill the gaps by studying the PTMs of a small representative chemotactic cytokine, RANTES. RANTES can inhibit HIV-1 infection by competing with it for binding to receptor CCR5 and stimulating CCR5 endocytosis. Unfortunately, RANTES can induce strong signaling, leading to severe inflammatory side effects. We apply a chemical biology approach to explore the potential of post-translationally modified RANTES as safe inhibitors of HIV-1 infection. We synthesized and systematically tested a library of RANTES isoforms for their ability to inhibit inflammatory signaling and prevent HIV-1 infection of primary human cells. Through this research, we revealed that most of the glycosylated variants have decreased inflammation-associated properties and identified one particular glyco variant, a truncated RANTES containing a Galβ1-3GalNAc disaccharide α-linked to Ser4, which stands out as having the best overall properties: relatively high HIV-1 inhibition potency but also weak inflammatory properties. Moreover, our results provided a structural basis for the observed changes in the properties of RANTES. Taken together, this work highlights the potential importance of glycosylation as an alternative strategy for developing CCR5 inhibitors to treat HIV-1 infection and, more generally, for reducing or eliminating unwanted properties of therapeutic proteins.

Fibers have been widely used for wearable textiles and fiber-reinforced composites owing to their unique structures and performances. However, design and fabrication of 1D advanced fiber materials with diversified surface microstructures and desired functionalities is still a considerable challenge. In this study, we present a novel one-dimensional confined breath figure (1D-cBF) approach for efficient preparation of a brand-new kind of 1D continuous fibers surface-engineered with conformal honeycomb porous microstructures (F@HPMs) and a novel kind of Hybrid F@HPMs (HF@HPMs) with functional nanomaterials incorporated in porous microstructures. The obtained F@HPMs demonstrated controllable surface microstructural morphologies by adjusting the experimental variables, and the main influential factors including solvents, concentrations, polymer bricks, and substrates in the 1D-cBF process were systematically studied. Moreover, various functional nanocomponents could be incorporated for developing HF@HPMs for customized functionalities. As a demonstration, TiO2/HF@HPMs that incorporate with TiO2 nanoparticles were fabricated for enhanced photodegradation of organic pollutants.

Protein O-glycosylation is a diverse, common, and important post-translational modification of both proteins inside the cell and those that are secreted or membrane-bound. Much work has shown that O-glycosylation can alter the structure, function, and physical properties of the proteins to which it is attached. One gap remaining in our understanding of O-glycoproteins is how O-glycans might affect the folding of proteins. Here, we took advantage of synthetic, homogeneous O-glycopeptides to show that certain glycosylation patterns have an intrinsic effect, independent of any cellular folding machinery, on the folding pathway of a model O-glycoprotein, a carbohydrate binding module (CBM) derived from the Trichoderma reesei cellulase TrCel7A. The strongest effect, a 6-fold increase in overall folding rate, was observed when a single O-mannose was the glycan, and the glycosylation site was near the N-terminus of the peptide sequence. We were also able to show that glycosylation patterns affected the kinetics of each step in unique ways, which may help to explain the observations made here. This work is a first step toward quantitative understanding of how O-glycosylation might control, through intrinsic means, the folding of O-glycoproteins. Such an understanding is expected to facilitate future investigations into the effects of glycosylation on more biological processes related to protein folding.

Phosphorylation of the N-terminal transactivation domain (TAD) of tumor suppressor p53 (p53TAD) helps regulate many of p53’s biological functions. Chemical synthesis of the p53TAD sequence with various phosphorylation patterns, through native chemical ligation and metal-free desulfurization, would facilitate studies of p53TAD phosphorylation and its role in regulating p53 function. Here, unphosphorylated, mono- and pentaphosphorylated p53TAD constructs were chemically synthesized. During the synthesis, methionine oxidation was found to be a serious problem and reduction was required at different stages, according to the number of phosphorylation sites.

Protein glycosylation has been shown to have a variety of site-specific and glycan-specific effects, but so far, the molecular logic that leads to such observations has been elusive. Understanding the structural changes that occur and being able to correlate those with the physical properties of the glycopeptide are valuable steps toward being able to predict how specific glycosylation patterns will affect the stability of glycoproteins. By systematically comparing the structural features of the O-glycosylated carbohydrate-binding module of a Trichoderma reesei-derived Family 7 cellobiohydrolase, we were able to develop a better understanding of the influence of O-glycan structure on the molecule's physical stability. Our results indicate that the previously observed stabilizing effects of O-glycans come from the introduction of new bonding interactions to the structure and increased rigidity, while the decreased stability seemed to result from the impaired interactions and increased conformational flexibility. This type of knowledge provides a powerful and potentially general mechanism for improving the stability of proteins through glycoengineering.

SH2 domains recognize phosphotyrosine (pY)-containing peptide ligands and play key roles in the regulation of receptor tyrosine kinase pathways. Each SH2 domain has individualized specificity, encoded in the amino acids neighboring the pY, for defined targets that convey their distinct functions. The C-terminal SH2 domain (PLCC) of the phospholipase C-γ1 full-length protein (PLCγ1) typically binds peptides containing small and hydrophobic amino acids adjacent to the pY, including a peptide derived from platelet-derived growth factor receptor B (PDGFRB) and an intraprotein recognition site (Y783 of PLCγ1) involved in the regulation of the protein's lipase activity. Remarkably, PLCC also recognizes unexpected peptides containing amino acids with polar or bulky side chains that deviate from this pattern. This versatility in recognition specificity may allow PLCγ1 to participate in diverse, previously unrecognized, signaling pathways in response to binding chemically dissimilar partners. We have used structural approaches, including nuclear magnetic resonance and X-ray crystallography, to elucidate the mechanisms of noncognate peptide binding to PLCC by ligands derived from receptor tyrosine kinase ErbB2 and from the insulin receptor. The high-resolution peptide-bound structures reveal that PLCC has a relatively static backbone but contains a chemically rich protein surface comprised of a combination of hydrophobic pockets and amino acids with charged side chains. We demonstrate that this expansive and chemically diverse PLCC interface, in addition to peptide conformational plasticity, permits PLCC to recognize specific noncognate peptide ligands with multimodal specificity.

With the rapid advancement in wearable electronics, energy harvesting devices based on triboelectric nanogenerators (TENGs) have been intensively investigated for providing sustainable power supply for them. However, the fabrication of wearable TENGs still remains great challenges, such as flexibility, breathability and washability. Here, a route to develop a new kind of woven-structured triboelectric nanogenerator (WS-TENG) with a facile, low-cost, and scalable electrospinning technique is reported. The WS-TENG is fabricated with commercial stainless-steel yarns wrapped by electrospun polyamide 66 nanofiber and poly(vinylidenefluoride-co-trifluoroethylene) nanofiber, respectively. Triggered by diversified friction materials under a working principle of freestanding mode, the open-circuit voltage, short-circuit current and maximum instantaneous power density from the WS-TENG can reach up to 166 V, 8.5 µA and 93 mW/m2, respectively. By virtue of high flexibility, desirable breathability, washability and excellent durability, the fabricated WS-TENG is demonstrated to be a reliable power textile to light up 58 light-emitting diodes (LED) connected serially, charge commercial capacitors and drive portable electronics. A smart glove with stitched WS-TENGs is made to detect finger motion in different circumstances. The work presents a new approach for self-powered textiles with potential applications in biomechanical energy harvesting, wearable electronics and human motion monitoring.

Electrospun polyamide (PA) 66 nanofiber bundles with high conductivity, improved strength, and robust flexibility were successfully manufactured through simply adsorbing multiwall carbon nanotubes (MWNTs) on the surface of electrospun PA66 nanofibers. The highest electrical conductivity (0.2 S/cm) and tensile strength (103.3 MPa) were achieved for the bundles immersed in the suspension with 0.05 wt % MWNTs, indicating the formation of conductive network from adsorbed MWNTs on the surface of PA66 nanofibers. The decrease of porosity for the bundles immersed in the MWNT dispersion and the formation of hydrogen bond between PA66 nanofibers and MWNTs suggest a superb interfacial interaction, which is responsible for the excellent mechanical properties of the nanocomposite bundles. Furthermore, the resistance fluctuation under bending is less than 3.6%, indicating a high flexibility of the nanocomposite bundles. The resistance of the nanocomposite bundle had a better linear dependence on the temperature applied between 30 and 150 °C. More importantly, such highest working temperature of 150 °C far exceeded that of other polymer-based temperature sensors previously reported. This suggests that such prepared MWNTs-adsorbed electrospun PA66 nanofiber bundles have great potentials in high temperature detectors.

Flexible piezoelectric nanogenerators (FPENGs) have attracted a great attention owing to their promising applications in harvesting mechanical energy and driving portable devices. To develop high-performance FPENGs, the significant relationship among material, structure and performance inspired us a rational design of FPENGs from Pdop-BaTiO3@P(VDF-TrFE) nanocomposite fiber mats with a hierarchically architected microstructure. In contrast with previous approaches, the polydopamine (Pdop) modified barium titanate (BaTiO3, BT) nanoparticles have been anchored onto the surface of electrospun poly (vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) fibers to fabricate hierarchical micro-structured membrane in this study, which not only effectively avoids the agglomeration of nanofillers but also enhances the density of interfaces in the nanocomposites. As a result, the as-fabricated FPENGs show a significantly enhanced output of 6 V and 1.5 μA as compared to the PENG with only P(VDF-TrFE) membrane (1.25 V and 0.6 μA). Furthermore, output voltage of the new FPENGs is 40%–68% higher than that of composite membranes with nanoparticles at the interior of nanofibers. The improved output of the PENG is attributed to the high density of interfaces in the hierarchical microstructure and the corresponding enhancement of dielectric response. Then, electric performance of FPENGs was investigated in terms of force, frequency and load resistance. Finally, the FPENG was employed to efficiently detect human body movements as self-powered sensors. The hierarchical nanocomposite membrane designed in this study provides an effective approach for developing mechanical energy harvesters, wearable sensor network and self-powered devices.

Protein glycosylation is one of the most common post-translational modifications and can influence many properties of proteins. Abnormal protein glycosylation can lead to protein malfunction and serious disease. While appreciation of glycosylation's importance is growing in the scientific community, especially in recent years, a lack of homogeneous glycoproteins with well-defined glycan structures has made it difficult to understand the correlation between the structure of glycoproteins and their properties at a quantitative level. This has been a significant limitation on rational applications of glycosylation and on optimizing glycoprotein properties. Through the extraordinary efforts of chemists, it is now feasible to use chemical synthesis to produce collections of homogeneous glycoforms with systematic variations in amino acid sequence, glycosidic linkage, anomeric configuration, and glycan structure. Such a technical advance has greatly facilitated the study and application of protein glycosylation. This Perspective highlights some representative work in this research area, with the goal of inspiring and encouraging more scientists to pursue the glycosciences.

Diabetes is a leading cause of death worldwide and results in over 3 million annual deaths. While insulin manages the disease well, many patients fail to comply with injection schedules and, despite significant investment, a more convenient oral formulation of insulin is still unavailable. Studies suggest that glycosylation may stabilize peptides for oral delivery but the demanding production of homogeneously glycosylated peptides has hampered transition into the clinic. We report here the first total synthesis of homogeneously glycosylated insulin. After characterizing a series of insulin glycoforms with systematically varied O-glycosylation sites and structures, we demonstrate that O-mannosylation of insulin B-chain Thr27 reduces the peptide’s susceptibility to proteases and self-association, both critical properties for oral dosing, while maintaining full activity. This work illustrates the promise of glycosylation as a general mechanism for regulating peptide activity and expanding their therapeutic use.

Electrospun polyamide PA 66 nanofiber bundles were mechanically strengthened via compositing with polyvinyl alcohol (PVA). The highest tensile strength (126.4 MPa) was achieved for the bundles immersed in the solution with 5.0 wt% PVA, indicating sufficient PVA filling between nanofibers after drying the impregnated nanofiber bundles. The disappearance of voids for the bundles immersed in the PVA solution indicated a superb interface adhesion, which was responsible for the excellent mechanical properties of the composite bundles. Furthermore, the step-cycle and stress relaxation tests were carried out to shed light on the deformation evolution and the viscous stress of the bundles. The results further demonstrated the excellent mechanical properties of the composite bundles.

Protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. Going forward, this study suggests the possibility of designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.

SH2B1 is a multidomain protein that serves as a key adaptor to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either by a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY. This specificity for chemically disparate species suggests that SH2B1 relies on distinct thermodynamic or structural mechanisms to bind to peptides. Using binding and structural strategies, we have identified unique thermodynamic signatures for each peptide binding mode, and several SH2B1 residues, including K575 and R578, that play distinct roles in peptide binding. The high-resolution structure of the SH2 domain of SH2B1 further reveals conformationally plastic protein loops that may contribute to the ability of the protein to recognize dissimilar ligands. Together, numerous hydrophobic and electrostatic interactions, in addition to backbone conformational flexibility, permit the recognition of diverse peptides by SH2B1. An understanding of this expanded peptide recognition will allow for the identification of novel physiologically relevant SH2B1/peptide interactions, which can contribute to the design of obesity and diabetes pharmaceuticals to target the ligand-binding interface of SH2B1 with high specificity.

Human galanin-like peptide (hGALP) is a newly discovered hypothalamic peptide that plays important roles in the regulation of food intake and energy balance. Here, we demonstrate that the aspartic acid ligation can be employed to achieve an efficient synthesis of hGALP. The total synthesis of hGALP enhances our ability to study its biology and facilitates the development of more stable analogues.

Cyclization reactions of ethyl 2-(2-hydroxyaryl)-2-oxoacetates with ethyl 2,3-butadienoate and allenylsulfone proceeded smoothly in the presence of tertiary phosphine and sodium p-toluenesulfinate (SPTS) to give the corresponding quaternary carbon centered chromans in moderate to good yields under mild conditions, which provides an alternative efficient approach for the synthesis of biologically active chroman products.

Treatment of pyridine and dimethyl acetylenedicarboxylate derivatives with N-substituted isatylidene derivatives resulted in three-component condensations, affording 1′,9a′-dihydrospiro[indoline-3,2-quinolizin]-2-one derivatives in high yields and with good diastereoselectivities through 1,4-dipolar cycloadditions.

The 1,4-diazabicyclic[2.2.2]octane (DABCO)-catalyzed intermolecular Rauhut-Currier reaction of maleimides with electron-deficient allenes has been investigated, affording the corresponding products in good to high yields under mild conditions. The first example of a β-isocupreidine (β-ICD)-catalyzed highly enantioselective intermolecular Rauhut-Currier reaction of maleimides with allenoates and penta-3,4-dien-2-one has been also developed, allowing the synthesis of optically active functionalized allene derivatives in good to high yields along with good to excellent enantioselectivities.

The phosphane-catalyzed umpolung addition of various nucleophiles to ethyl 2-methyl-2,3-butadienoate is described. Oxygen, nitrogen, and carbon nucleophiles smoothly reacted with ethyl 2-methyl-2,3-butadienoate to give the corresponding umpolung addition products in good to excellent yields by a similar reaction mechanism. For sulfur nucleophiles, the addition reactions with ethyl 2-methyl-2,3-butadienoate proceeded by a different mechanism.

In the presence of triphenylphosphine, the reactions of N-protected imines or their precursors with DEAD proceeded smoothly to give the corresponding functionalized 1H-1,2,4-triazole-1,4(5H)-dicarboxylate derivatives in good to high yields under mild conditions. A plausible mechanism has been proposed on the basis of the control experiments.

P(n)Bu(3)-catalyzed cyclization reactions of salicylaldimines and salicylaldehydes with ethyl 2,3-butadienoate gave the corresponding functionalized chromans in moderate to good yields in THF under mild conditions. The new reaction provides a new method for the synthesis of biologically active chroman products.

DABCO-catalyzed aza-MBH reactions of N-Boc imines with MVK and EVK have been thoroughly investigated in the paper. The asymmetric version of this aza-MBH reaction was also systematically investigated by using a chiral amine or a chiral phosphane catalyst. It was found that most of the N-protected imines are suitable substrates under the mild reaction conditions and are able to give the corresponding adducts in moderate yields with high ee values. The TQO- or LB1-catalyzed aza-MBH reactions of N-protected α-amidoalkyl phenyl sulfones or α-amidoalkyl p-tolyl sulfones with MVK could be well conducted, which provides a facile and direct route to obtain highly enantioselective aza-MBH adducts. The Boc protecting group of the aza-MBH product could be easily removed under acidic conditions to give the corresponding α-methylene-β-amino ketone or α-methylene-β-amino alcohol derivatives in good yields.

Lewis base catalyzed reactions of N-Boc-imines and ethyl 2,3-butadienoate were investigated systematically. The normal aza-Morita-Bylis-Hillman products were obtained in good to excellent yields catalyzed by DABCO. When PPh(3) was used as the catalyst, novel rearrangement product (E)-ethyl 2-((Z)-(tert-butoxycarbonylimino)(aryl)methyl)but-2-enoates could be formed in moderate yields.

A series of chiral sterically congested phosphane-amide bifunctional Lewis bases L1-L3 have been successfully synthesized and their application in asymmetric aza-Morita-Baylis-Hillman (aza-MBH) reactions of N-sulfonated imines with activated olefins such as methyl and ethyl vinyl ketone has been investigated under mild conditions. The corresponding aza-MBH adducts can be obtained in good-to-excellent yields (up to 98%) and moderate-to-good enantioselectivities (up to 91 or 93 % ee) in dichloromethane at room temperature (20 degrees C) with these novel chiral bifunctional phosphane Lewis bases. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

UNLABELLED Family 1 carbohydrate-binding modules (CBMs) are ubiquitous components of multimodular fungal enzymes that degrade plant cell wall polysaccharides and bind specifically to cellulose. Native glycosylation of family 1 CBMs has been shown to substantially impact multiple physical properties, including thermal and proteolytic stability and cellulose binding affinity. To gain molecular insights into the changes in CBM properties upon glycosylation, solution structures of two glycoforms of a Trichoderma reesei family 1 CBM were studied by NMR spectroscopy: a glycosylated family 1 CBM with a mannose group attached to both Thr1 and Ser3 and a second family 1 CBM with single mannose groups attached to Thr1, Ser3 and Ser14. The structures clearly reveal that monosaccharides at both Ser3 and Ser14 on family 1 CBMs present additional cellulose binding platforms, similar to well-characterized aromatic residues at the binding interface, which align to the cellulose surface. These results are in agreement with previous experimental work demonstrating that glycans at Ser3 and Ser14 impart significant improvements in binding affinity. Additionally, detailed analysis of the NMR structures and molecular simulations indicates that the protein backbone of the CBM is not significantly altered by attachment of monosaccharides, and that the mannose attached to Ser14 may be more flexible than the mannose at Ser3. Overall, the present study reveals how family 1 CBM structures are affected by covalent attachment of monosaccharides, which are likely important post-translational modifications of these common subdomains of fungal plant cell wall degrading enzymes. DATABASE Structural data have been deposited in the RCSB Protein Data Bank (PDB codes: 2MWJ and 2MWK) and the BioMagRes Bank (BMRB codes: 25331 and 25332) for CBM_M2 and CBM_M3, respectively.

The importance of the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage in controlling the effects of CBM O-glycosylation is shown., Protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. Going forward, this study suggests the possibility of designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.

Chemical protein synthesis is a useful tool to generate pure proteins which are otherwise difficult to obtain in sufficient amounts for structure and property analysis. Additionally, because of the precise and flexible nature of chemical synthesis, it allows for controllable variation of protein sequences, which is valuable for understanding the relationships between protein structure and function. Despite the usefulness of chemical protein synthesis, it has not been widely adopted as a tool for protein characterization, mainly because of the lack of general and efficient methods for the preparation and coupling of peptide fragments and for the folding of polypeptide chains. To address these issues, many new methods have recently been developed in the areas of solid-phase peptide synthesis, peptide fragment assembly, and protein folding. Here we review these recent technological advances and highlight the gaps needing to be addressed in future research.

Chemical protein synthesis is a useful tool to generate pure proteins which are otherwise difficult to obtain in sufficient amounts for structure and property analysis. Additionally, because of the precise and flexible nature of chemical synthesis, it allows for controllable variation of protein sequences, which is valuable for understanding the relationships between protein structure and function. Despite the usefulness of chemical protein synthesis, it has not been widely adopted as a tool for protein characterization, mainly because of the lack of general and efficient methods for the preparation and coupling of peptide fragments and for the folding of polypeptide chains. To address these issues, many new methods have recently been developed in the areas of solid-phase peptide synthesis, peptide fragment assembly, and protein folding. Here we review these recent technological advances and highlight the gaps needing to be addressed in future research.

Cyclization reactions of ethyl 2-(2-hydroxyaryl)-2-oxoacetates with ethyl 2,3-butadienoate and allenylsulfone proceeded smoothly in the presence of tertiary phosphine and sodium p-toluenesulfinate (SPTS) to give the corresponding quaternary carbon centered chromans in moderate to good yields under mild conditions, which provides an alternative efficient approach for the synthesis of biologically active chroman products.

In the presence of the quinidine-derived β-isocupreidine as organocatalyst, the products are obtained with good to high e.e.

Precursors of imines or N-protected imines react with dialkylazodicarboxylate in the presence of PPh3 to give the corresponding functionalized 1H-1,2,4-triazole dicarboxylate derivatives.