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In healthy eyes, the tear film lipid layer (TFLL) is considered to act as an evaporation resistant barrier, which prevents eyes from drying. Seeking to understand the mechanisms behind the evaporation resistance of the TFLL, we studied mixtures of lipid layer wax esters and O-acyl-omega-hydroxy fatty acids. Analyzing their self-assembly and biophysical properties led to new discoveries concerning the structure and function of the TFLL. We discovered how these lipids self-assemble at the air-water interface and form an efficient antievaporative barrier, demonstrating for the first time how the interaction of different tear film lipid species can improve the evaporation resistance compared with individual lipid classes on their own. These results provide a potential mechanism for the evaporation resistance of the lipid layer. In addition, the results serve as a base for the future development of improved dry eye treatments and other applications where the evaporation of water represents a significant challenge.

Glucose-and sodium-dependent glucose transporters (GLUTs and SGLTs) play vital roles in human biology. Of the 14 GLUTs and 12 SGLTs, the GLUT1 transporter has gained t h e most widespread recognition because GLUT1 is overexpressed in several cancers and is a clinically valid therapeutic target. We have been pursuing a GLUT1-targeting approach in boron neutron capture therapy (BNCT). Here, we report on surprising findings encountered w i t h a set of 6-deoxy-6-thio-carbora n y l D-glucoconjugates. In more detail, we show that even subtle structural changes in t h e carborane cluster, and the linker, may significantly reduce the delivery capacity of GLUT1-based boron carriers. In addition to providing new insights on the substrate specificity of this important transporter, we reach a fresh perspec t i v e on the boundaries within which a GLUT1-targeting approach in BNCT can be further refined.

Halogenation can be utilized for the purposes of labeling and molecular imaging, providing a means to, e.g., follow drug distribution in an organism through positron emission tomography (PET) or study the molecular recognition events unfolding by nuclear magnetic resonance (NMR) spectroscopy. For cancer therapeutics, where often highly toxic substances are employed, it is of importance to be able to track the distribution of the drugs and their metabolites in order to ensure minimal side effects. Labeling should ideally have a negligible disruptive effect on the efficacy of a given drug. Using a combination of NMR spectroscopy and cytotoxicity assays, we identify a site susceptible to halogenation in monomethyl auristatin F (MMAF), a widely used cytotoxic agent in the antibody-drug conjugate (ADC) family of cancer drugs, and study the effects of fluorination and chlorination on the physiological solution structure of the auristatins and their cytotoxicity. We find that the cytotoxicity of the parent drug is retained, while the conformational equilibrium is shifted significantly toward the biologically active trans isomer, simultaneously decreasing the concentration of the inactive and potentially disruptive cis isomer by up to 50%. Our results may serve as a base for the future assembly of a multifunctional toolkit for the assessment of linker technologies and exploring bystander effects from the warhead perspective in auristatin-derived ADCs.

Correction: 10.1021/acs.joc.1c02513. The tear film lipid layer (TFLL) that covers the ocular surface contains several unique lipid classes, including O-acyl-omega-hydroxy fatty acids, type I-St diesters, and type II diesters. While the TFLL represents a unique biological barrier that plays a central role in stabilizing the entire tear film, little is known about the properties and roles of individual lipid species. This is because their isolation from tear samples in sufficient quantities is a tedious task. To provide access to these species in their pure form, and to shed light on their properties, we here report a general strategy for the synthesis and structural characterization of these lipid classes. In addition, we study the organization and behavior of the lipids at the air-tear interface. Through these studies, new insights on the relationship between structural features, such as number of double bonds and the chain length, and film properties, such as spreading and evaporation resistance, were uncovered.

Glucose- and sodium-dependent glucose transporters (GLUTs and SGLTs) play vital roles in human biology. Of the 14 GLUTs and 12 SGLTs, the GLUT1 transporter has gained the most widespread recognition because GLUT1 is overexpressed in several cancers and is a clinically valid therapeutic target. We have been pursuing a GLUT1-targeting approach in boron neutron capture therapy (BNCT). Here, we report on surprising findings encountered with a set of 6-deoxy-6-thio-carboranyl d-glucoconjugates. In more detail, we show that even subtle structural changes in the carborane cluster, and the linker, may significantly reduce the delivery capacity of GLUT1-based boron carriers. In addition to providing new insights on the substrate specificity of this important transporter, we reach a fresh perspective on the boundaries within which a GLUT1-targeting approach in BNCT can be further refined.

Purpose of the study: Explore perceptions, expectations and challenges following a telerehabilitation programme using augmented reality glasses (ARG) in patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) or recently diagnosed myocardial infarction (MI). Materials and Methods: A qualitative approach was employed to track perspectives from a range of patients with chronic lung and/or heart diseases. COPD, IPF and MI outpatients from Denmark and Finland were invited to participate. Data were collected through focus group and semi-structured in-depth interviews. Qualitative analysis was performed using standard thematic analytical approaches. A topic guide was used to explore experiences and perceptions of the ARG telerehabilitation device among participants. Results: Thirteen patients (4 MI, 2 IPF and 7 COPD), 3 women and 10 men aged 56 to 75 years (mean age 63.3 years) were allocated into one focus group (9 patients) and 4 interviews (4 patients). Twelve patients reported the added value of ARG and suggested constructive changes such as the adjustable screen/brightness, robust head fixation for exercise performance, easy to navigate interface and supported feedback based on exercise performance. Conclusion: Patients with chronic heart or lung diseases described the added value in an ARG telerehabilitation programme. Improvements for a future version of the ARG were suggested.IMPLICATIONS FOR REHABILITATION Patients with chronic pulmonary and heart diseases have difficulties to change behaviour to a more active and healthy lifestyle, offers from the health sector to participate in rehabilitation programmes at the hospital are feasible and improves quality of life and exercise capacity. Not all the patients are capable of participating in such rehabilitation programmes due to frailty and long distance to the hospital. Telerehabilitation seems to be a potential treatment to cope with the needs expressed above. Patient involvement in the development of a telerehabilitation solution to empower chronic pulmonary and heart patients to train, ensures a positive contribution to the design of the expected augmented reality software and hardware envisioned solution for telerehabilitation. The development of a user-centered telerehabilitation platform responding to the preferences of patients with chronic disease will remove barriers that limit use and compliance and improve empowerment in future research projects.

In healthy eyes, the tear film lipid layer (TFLL) is considered to act as an evaporation resistant barrier, which prevents eyes from drying. Seeking to understand the mechanisms behind the evaporation resistance of the TFLL, we studied mixtures of lipid layer wax esters and

Monomethyl auristatin E and monomethyl auristatin F are widely used cytotoxic agents in antibody-drug conjugates (ADCs), a group of promising cancer drugs. The ADCs specifically target cancer cells, releasing the auristatins inside, which results in the prevention of mitosis. The auristatins suffer from a potentially serious flaw, however. In solution, the molecules exist in an equal mixture of two conformers, cis and trans. Only the trans-isomer is biologically active and the isomerization process, i.e., the conversion of cis to trans is slow. This significantly diminishes the efficiency of the drugs and their corresponding ADCs, and perhaps more importantly, raises concerns over drug safety. The potency of the auristatins would be enhanced by decreasing the amount of the biologically inactive isomer, either by stabilizing the transisomer or destabilizing the cis-isomer. Here, we follow the computer-aided design strategy of shifting the conformational equilibrium and employ high-level quantum chemical modeling to identify promising candidates for improved auristatins. Coupled cluster calculations predict that a simple halogenation in the norephedrine/phenylalanine residues shifts the isomer equilibrium almost completely toward the active trans-conformation, due to enhanced intramolecular interactions specific to the active isomer.

The aim of this study was to assess what properties of the pseudostationary phases in electrokinetic capillary chromatography affect the interactions between monomethyl auristatin E (MMAE) and hydrophilically modified structural analogues thereof with various lipophilic phases. MMAE is a widely used cytotoxic agent in antibody–drug conjugates (ADC), which are used as selective biopharmaceutical drugs in the treatment of cancers. MMAE and its derivatives are highly lipophilic, yet they fail to interact with biomimicking phosphatidylcholine–phosphatidylserine liposomes. To reveal what properties affect the interaction of the auristatin derivatives with cell plasma membrane-mimicking vesicles, capillary electrokinetic chromatography was used with four different types of micellar and vesicular pseudostationary phases: pure vesicles, mixed vesicles, mixed micelles, and pure micelles. Vesicular phases were composed of pure phospholipids [dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC)] and phospholipid–surfactant mixtures [sodium dodecyl sulfate, (SDS) with DMPC and DLPC] while the micellar phases comprised pure surfactant (SDS) and surfactant–phospholipid mixtures (SDS–DMPC and SDS–DLPC). In addition, differential scanning calorimetry and dynamic light scattering were used to monitor the aggregate composition. Our data shows that the interaction between hydrophobic auristatin derivatives and hydrophobic pseudostationary phases critically depends on the type, size, and hydrogen bonding capability of the pseudostationary phases.

The tear film lipid layer (TFLL) is important to the maintenance of ocular surface health. Surprisingly, information on the individual roles of the myriad of unique lipids found therein is limited. The most abundant lipid species are the wax esters (WE) and cholesteryl esters (CE), and, especially their branched analogs. The isolation of these lipid species from the TFLL has proved to be tedious, and as a result, insights on their biophysical profiles and role in the TFLL is currently lacking. Herein, we circumvent these issues by a total synthesis of the most abundant iso-methyl branched WEs and CEs found in the TFLL. Through a detailed characterization of the biophysical properties, by the use of Langmuir monolayer and wide-angle X-ray scattering techniques, we demonstrate that chain branching alters the behavior of these lipid species on multiple levels. Taken together, our results fill an important knowledge gap concerning the structure and function of the TFLL on the whole.

Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full harness of this potential come in the form of the suboptimal boron delivery strategies presently used in the clinics. To address these challenges, we have developed delivery agents that target the glucose transporter GLUT1. Here, we present the chemical synthesis of a number of

Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full harness of this potential come in the form of the suboptimal boron delivery strategies presently used in the clinics. To address these challenges, we have developed delivery agents that target the glucose transporter GLUT1. Here, we present the chemical synthesis of a number of ortho-carboranylmethyl-substituted glucoconjugates and the biological assessment of all positional isomers. Altogether, the study provides protocols for the synthesis and structural characterization of such glucoconjugates and insights into their essential properties, for example, cytotoxicity, GLUT1-affinity, metabolism, and boron delivery capacity. In addition to solidifying the biochemical foundations of a successful GLUT1-targeting approach to BNCT, we identify the most promising modification sites in d-glucose, which are critical in order to further develop this strategy toward clinical use.

Boron neutron capture therapy (BNCT) for cancer is on the rise worldwide due to recent developments of in-hospital neutron accelerators which are expected to revolutionize patient treatments. There is an urgent need for improved boron delivery agents, and herein we have focused on studying the biochemical foundations upon which a successful GLUT1-targeting strategy to BNCT could be based. By combining synthesis and molecular modeling with affinity and cytotoxicity studies, we unravel the mechanisms behind the considerable potential of appropriately designed glucoconjugates as boron delivery agents for BNCT. In addition to addressing the biochemical premises of the approach in detail, we report on a hit glucoconjugate which displays good cytocompatibility, aqueous solubility, high transporter affinity, and, crucially, an exceptional boron delivery capacity in the in vitro assessment thereby pointing toward the significant potential embedded in this approach.

Purpose The tear film lipid layer (TFLL) covers the tear film, stabilizing it and providing a protective barrier against the environment. The TFLL is divided into polar and non-polar sublayers, but the interplay between lipid classes in these sublayers and the structure-function relationship of the TFLL remains poorly characterized. This study aims to provide insight into TFLL function by elucidating the interactions between polar and non-polar TFLL lipids at the molecular level. Methods Mixed films of polar O-acyl-ω-hydroxy fatty acids (OAHFA) or phospholipids and non-polar cholesteryl esters (CE) were used as a model of the TFLL. The organization of the films was studied by using a combination of Brewster angle and fluorescence microscopy in a Langmuir trough system. In addition, the evaporation resistance of the lipid films was evaluated. Results Phospholipids and OAHFAs induced the formation of a stable multilamellar CE film. The formation of this film was driven by the interdigitation of acyl chains between the monolayer of polar lipids and the CE multilayer lamellae. Surprisingly, the multilayer structure was destabilized by both low and high concentrations of polar lipids. In addition, the CE multilayer was no more effective in resisting the evaporation of water than a polar lipid monolayer. Conclusions Formation of multilamellar films by major tear film lipids suggest that the TFLL may have a similar structure. Moreover, in contrast to the current understanding, polar TFLL lipids may not mainly act by stabilizing the non-polar TFLL sublayer, but through a direct evaporation resistant effect.

This review is the counterpart of a 2018 Chemical Reviews article that examined the mechanisms of chemical glycosylation in the absence of stereodirecting participation. Attention is now turned to a critical review of the evidence in support of stereodirecting participation in glycosylation reactions by esters from either the vicinal or more remote positions. As participation by esters is often accompanied by ester migration, the mechanism(s) of migration are also reviewed. Esters are central to the entire review, which accordingly opens with an overview of their structure and their influence on the conformations of six-membered rings. Next the structure and relative energetics of dioxacarbeniun ions are covered with emphasis on the influence of ring size. The existing kinetic evidence for participation is then presented followed an overview of the various intermediates either isolated or characterized spectroscopically. The evidence supporting participation from remote or distal positions is critically examined and alternative hypotheses for the stereodirecting effect of such esters is presented. The mechanisms of ester migration are first examined from the perspective of glycosylation reactions, and then more broadly in the context of partially acylated polyols.

The tear film lipid layer (TFLL) that covers the ocular surface contains several unique lipid classes, including

Soft nanoparticles are interesting materials due to their size, deformability, and ability to host guest molecules. Surface properties play an essential role in determining the fate of the particles in biological medium, and coating of the nanoparticles (and polymers) with carbohydrates has been found to be an efficient strategy for increasing their biocompatibility and fine-tuning other important properties such as aqueous solubility. In this work, soft nanogels of poly(N-vinylcaprolactam), PNVCL, were surface-functionalized with different glucose and maltose ligands, and the colloidal properties of the gels were analyzed. The PNVCL nanogels were first prepared via semibatch precipitation polymerization, where a comonomer, propargyl acrylate (PA), was added after preparticle formation. The aim was to synthesize “clickable” nanogels with alkyne groups on their surfaces. The nanogels were then functionalized with two separate azido-glucosides and azido-maltosides (containing different linkers) through a copper-catalyzed azide–alkyne cycloaddition (CuAAc) click reaction. The glucose and maltose bearing nanogels were thermoresponsive and shrank upon heating. Compared to the PNVCL–PA nanogel, the carbohydrate bearing ones were larger, more hydrophilic, had volume phase transitions at higher temperatures, and were more stable against salt-induced precipitation. In addition to investigating the colloidal properties of the nanogels, the carbohydrate recognition was addressed by studying the interactions with a model lectin, concanavalin A (Con A). The binding efficiency was not affected by the temperature, which indicates that the carbohydrate moieties are located on the gel surfaces, and are capable of interacting with other biomolecules independent of temperature. Thus, the synthesis produces nanogels, which have surface functions capable of biorelevant interactions and a thermoresponsive structure. These types of particles can be used for drug delivery.

Dry eye syndrome (DES) is a prevalent disease in which the tear film homeostasis is compromised. One of the main causes of DES is thought to be an alteration in the composition of the outermost layer of the tear film, the tear film lipid layer (TFLL), resulting in an increased evaporation of water from the tear film and subsequent drying of the ocular surface. Recent studies have suggested that the specific TFLL lipids, namely, O-aryl-omega-hydroxy fatty acids (OAHFAs) and diesters (DiEs), may play a role in the development of DES. However, their specific connection to DES has remained largely unknown until now because of the lack of information on their biophysical properties and their role in the TFLL. Herein, we have addressed this issue by studying the biophysical properties and evaporation resistance of a library containing 10 synthetic analogues of TFLL OAHFAs and DiEs. Our results show how the variations of chain length and polar groups affect the phase behavior of these lipids at the tear film surface. In addition, the results revealed that the OAHFAs exhibiting a liquid-expanded to solid phase transition formed films with high evaporation resistance, whereas the DiEs were found to have no evaporation resistance. Altogether, our results shed new light on the role of the OAHFAs and DiEs in the TFLL and their connection to DES, suggesting that OAHFAs are likely a key lipid class in maintaining the TFLL evaporation resistance.

Acetylated oligosaccharides are common in nature. While they are involved in several biochemical and biological processes, the role of the acetyl groups and the complexity of their migration has largely gone unnoticed. In this work, by combination of organic synthesis, NMR spectroscopy and quantum chemical modeling, we show that acetyl group migration is a much more complex phenomenon than previously known. By use of synthetic oligomannoside model compounds, we demonstrate, for the first time, that the migration of acetyl groups in oligosaccharides and polysaccharides may not be limited to transfer within a single monosaccharide moiety, but may also involve migration over a glycosidic bond between two different saccharide units. The observed phenomenon is not only interesting from the chemical point of view, but it also raises new questions about the potential biological role of acylated carbohydrates in nature.

Antibody-drug conjugates (ADCs) are promising state-of-the-art biopharmaceutical drugs for selective drug-delivery applications and the treatment of diseases such as cancer. The idea behind the ADC technology is remarkable as it combines the highly selective targeting capacity of monoclonal antibodies with the cancer-killing ability of potent cytotoxic agents. The continuous development of improved ADCs requires systematic studies on the nature and effects of warhead modification. Recently, we focused on the hydrophilic modification of monomethyl auristatin E (MMAE), the most widely used cytotoxic agent in current clinical trial ADCs. Herein, we report on the use of micellar electrokinetic chromatography (MEKC) for studying the hydrophobic character of modified MMAE derivatives. Our data reveal a connection between the hydrophobicity of the modified warheads as free molecules and their cytotoxic activity. In addition, MMAE-trastuzumab ADCs were constructed and evaluated in preliminary cytotoxic assays.

The quest for novel natural-like biomolecular probes that can be used to gain information on biological recognition events is of topical interest to several scientific areas. In particular, the recognition of carbohydrates by proteins modulates a number of important biological processes. These molecular recognition events are, however, difficult to study by the use of naturally occurring oligosaccharides and polysaccharides owing to their intrinsic structural heterogeneity and to the many technical difficulties encountered during the isolation of sufficient quantities of pure material for detailed structural and biological studies. Therefore, the construction of homogenous biomolecular probes that can mimic both the biophysical properties of polysaccharide backbones and the properties of bioactive oligosaccharide fragments are highly sought after. Herein, synthetic methodology for the construction of well-defined bioconjugates consisting of biologically relevant disaccharide fragments grafted onto a dextran backbone is presented, and a preliminary NMR spectroscopy study of their interactions with galectin-3 as a model lectin is conducted. The authors thank the Magnus Ehrnrooth foundation, the Ruth and Nils‐Erik Stenbäck foundation, Åbo Akademi University, and Turku Centre for Lifespan Research for financial support. Jarl Hemming at the Laboratory of Wood and Paper Chemistry at Åbo Akademi is thanked for technical assistance with the SEC/MALLS analysis. Leena Kaven‐Honka is thanked for preparing the C. albicans mannans. The group at CIC bioGUNE thanks Agencia Estatal de Investigacion and MINECO of Spain (CTQ2015‐64597‐C2‐1P and SEV‐2016‐0644 Severo Ochoa Excellence Acreditation) and the European Commission for the TOLLerant and GlycoVAX ITN projects. The authors acknowledge Prof. Francisco Javier Cañada‐Vicinay and Pablo Valverde for the acquisition of some NMR spectra and Dr. Filipa Marcelo for the generous gift of the plasmid of the hGal3 CRD.

The quest for novel natural-like biomolecular probes which can be utilized to gain information on biological recognition events is of topical interest to several scientific areas. In particular, the recognition of carbohydrates by proteins modulates a number of important biological processes. These molecular recognition events are, however, difficult to study by the use of naturally occurring oligosaccharides and polysaccharides due to their intrinsic structural heterogeneity as well as the many technical difficulties encountered during the isolation of sufficient quantities of pure material for detailed structural and biological studies. Therefore, the construction of homogenous biomolecular probes which would both mimic the biophysical properties of polysaccharide backbones and the properties of bioactive oligosaccharide fragments are highly sought after. Herein, we present a synthetic methodology for the construction of well-defined bioconjugates consisting of biologically relevant disaccharide fragments grafted onto a dextran backbone and conduct a preliminary NMR-spectroscopic study of their interactions with the model lectin galectin-3.

One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

Antibody-drug conjugates (ADCs) are emerging as a promising class of selective drug delivery systems in the battle against cancer and other diseases. The auristatins monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) appear as the cytotoxic drug in almost half of the state-of-the-art ADCs on the market or in late stage clinical trials. Here, we present the first complete NMR spectroscopic characterisation of these challenging molecules, and investigate their structural properties by a combined NMR and quantum chemical modelling approach. We find that in solution, half of the drug molecules are locked in an inactive conformation, severely decreasing their efficiency, and potentially increasing the risk of side-effects. Furthermore, we identify sites susceptible to future modification, in order to potentially improve the performance of these drugs.

Antibody–drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug-delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site-selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC. We envisioned that hydrophilic bifunctional chemical linkers based on carbohydrates would be a useful class of derivatization agents for the construction of linker–drug conjugates and ADCs. Herein we describe the synthesis of carbohydrate-based derivatization agents, glycolinker–drug conjugates featuring the tubulin inhibitor monomethyl auristatin E and an ADC based on an anti-EGFR antibody. In addition, an initial in vitro cytotoxicity evaluation of the individual components and the ADC is provided against EGFR-positive cancer cells.

Many different glycoconjugates, including saponins (e.g., hellebrin) and anthracyclines (e.g., doxorubicin), are known to display cytotoxic activities. In recent work, we have developed synthetic protocols for the synthesis of various glycoconjugates, focusing on glycosylation methods for different classes of biomolecules. Simultaneously a number of saponins and anthracyclines have been generated. In this note, the cytotoxic activities of these synthesized compounds are briefly addressed.

Galactoglucomannan (GGM) is a polysaccharide mainly consisting of mannose, glucose, and galactose. GGM is the most abundant hemicellulose in the Norway spruce (Picea abies), but is also found in the cell wall of flax seeds, tobacco plants, and kiwifruit. Although several applications for GGM polysaccharides have been developed in pulp and paper manufacturing and the food and medical industries, attempts to synthesize and study distinct fragments of this polysaccharide have not been reported previously. Herein, the synthesis of one of the core trisaccharide units of GGM together with a less-abundant tetrasaccharide fragment is described. In addition, detailed NMR spectroscopic characterization of the model compounds, comparison of the spectral data with natural GGM, investigation of the acetyl-group migration phenomena that takes place in the polysaccharide by using small model compounds, and a binding study between the tetrasaccharide model fragment and a galactose-binding protein (the toxin viscumin) are reported.

A method for the glycosylation of anthracyclines featuring benzoylated imidate donors has been developed and utilized in the synthesis of glycosylated 4-deoxy-ε-rhodomycinone derivatives. Due to its high efficiency, regioselectivity, stereoselectivity, and operational simplicity, the method should prove valuable to researchers working with glycosylation of tetracyclic compounds.

Hellebrin and transvaalin are two naturally occurring saponins with biological activity. In the present paper, we describe a high yielding route to the synthesis and coupling of their shared glycone, scillabiose, to a model steroid. A convergent coupling strategy utilizing a scillabiose-based glycosyl donor was devised for the glycosylation. This convergent approach is appealing due to its high efficiency and simple deprotection procedure and may find further use in total synthesis of naturally occurring saponins and related compounds sharing the same glycone. Due to the widespread occurrence of this glycone in nature, the complete NMR spectroscopic characterization of all compounds prepared herein is provided as reference material. In addition, glycosylations were performed with the monosaccharide constituents of scillabiose, thereby providing a limited series of glycosylated steroids for potential future evaluation of the effects of the glycone on the overall biological activity.

Glycosylated steroids, such as cardenolides and saponins, are widely distributed in nature and have been shown to possess various types of biological activities. In the present study, carbohydrate donors were evaluated for the glycosylation of steroids; the results show that benzoylated imidate donors were superior in terms of efficiency and operational simplicity. These donors were then applied to the synthesis of a limited library of estradiol-based glycosteroid mimics containing a modified D-ring. The deprotected molecules contained three types of variations in the steroid backbone and four types of variations in the sugar moiety. The synthesized structures will be screened for biological activity and for their potential use in drug delivery systems.

Fully acetylated D- and L-α-mannosylacetaldehydes have been prepared and used as substrates to produce the corresponding cyanohydrins or cyanohydrin acetates with (2S) or (2R) configuration, respectively, at the cyanohydrin moiety. The (R)-oxynitrilase-catalysed synthesis and lipase-catalysed diastereomeric kinetic and dynamic kinetic resolutions were investigated. Sequential catalysis with almond meal [an economic source of (R)-oxynitrilase] and Burkholderia cepacia lipase was shown to be a straightforward method that yielded the four diastereomeric target cyanohydrins, the absolute configurations of which were confirmed by 1 H NMR analysis.

A convenient semi-synthesis of ( 8R , 8 ′ R )-matairesinol 4,4′-di- O -β- d -glucopyranoside (MDG), found in the stems of Trachelospermum asiaticum var. intermedium , is described starting from the readily available starting materials d -glucose and hydroxymatairesinol. By this approach the synthesis of MDG can be accomplished in six steps with an overall yield of 28%. In addition, the first complete NMR-spectroscopic characterization of MDG was accomplished by the combination of standard NMR techniques and spectral simulations performed with the PERCH NMR simulation software.

β-(1→2)-Linked oligomannosides constitute an important class of carbohydrate structures located on the cell surface of several Candida species, including C. albicans. As a result of the immunostimulating properties of such compounds, the upscaling of their synthesis is relevant. In this paper, a highly stereoselective synthesis of β-(1→2)-linked oligomannosides was performed by further development of and modifications to the methodologies described earlier in the literature. In addition to the synthesis of fully deprotected β-(1→2)-linked mannobiose and mannotriose, some preliminary modifications to the oligosaccharide core, resulting in close analogues with biological potential, are presented. The fully deprotected products form potential targets for screening against C. albicans and may also result in new model structures for vaccine development.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Several studies have implicated (1→2)-linked mannans as biologically relevant compounds. Recently, there has been a growing interest in the synthesis of multivalent carbohydrate assemblies due to their ability to target multiple receptors simultaneously. In the present work, a protective group strategy, based on the methodology originally developed by Crich, has been utilized for the homodimerization of olefinic carbohydrates, allowing a highly diastereoselective synthesis of some divalent structures. Furthermore, it is shown that divalent donors may undergo coupling reactions without losses in stereoselectivity or efficiency. The strategies described may potentially be applied to the synthesis of diverse neoglycoconjugates and oligosaccharides.

The European Space Agency's Soil Moisture and Ocean Salinity satellite comprises a single payload instrument known as the Microwave Interferometric Radiometer with Aperture Synthesis (MIRAS) coupled to a PROTEUS platform. MIRAS synthesizes a large aperture from a reasonably sized 2-D array of passive microwave radiometers. By using interferometric techniques, the required coverage and spatial resolution can be achieved without the need for a large antenna. This paper describes the MIRAS instrument, its observation modes, the imaging geometry, and data products.

A rapid, simple, and efficient deprotection procedure for the deprotection of benzyl- and/or benzylidene protected carbohydrates is described utilizing a continuous flow hydrogenation reactor. The method tolerates both acid- and base sensitive functional groups. The high efficiency, simple work-up, and short reaction time should make this method appealing to researchers working in the fields of carbohydrate chemistry and total synthesis.

9 p.-2 tab.-6 fig., Phosphorylated β-(1→2)-oligomannosides are found on the cell surface of several Candida species, including Candida albicans (an opportunistic pathogen). These molecules are believed to take part in the invasion process of fungal infections, which in the case of C. albicans can lead to severe bloodstream infections and death, and can therefore be considered important from a biological standpoint. Understanding the mechanism of their action requires access to the corresponding oligosaccharide model compounds in pure form. In the present work, synthesis of the model core structures involved in the invasion process of C. albicans, consisting of phosphorylated β-(1→2)-linked mannotriose and tetraose, is reported. In order to elucidate the nature of these molecules in more detail, an extensive NMR-spectroscopic study encompassing complete spectral characterization, conformational analysis and molecular modelling was performed. The obtained results were also compared to similar chemical entities devoid of the charged phosphate group., The authors thank the Academy of Finland (Research Grant #252371) and Stiftelsens för Åbo Akademi Forskningsinstitut for financial support. The CMST COST Action CM1102 Multivalent Glycosystems for Nanoscience—MultiGlycoNano is thanked for STSM funding to J.R., who also further acknowledges Suomalaisten Kemistien Seura for Young Scientist Award granted for his M.Sc. thesis work based on this study.

Immunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans ofCandida albicanswere evaluatedin vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

This paper describes the RETE (Research on Electrodynamic Tether Effects) experiment mounted on board the TSS (Tethered-Satellite System) satellite which was deployed on a cable from the space Shuttle Atlantis during the TSS mission flown in August 1992. The experiment layout and its modes of operation are described in detail. To give an idea of RETE capabilities and actual performance during the mission, samples of measurements are also presented.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first identified among a Swedish kindred with 17 cases. The average age of onset was 36 years. Autopsy in four cases revealed the presence of axonal spheroids. The causative gene is unknown.We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone-interviewed, and one of the original HDLS cases from 1984 was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied.Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS in 1984, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, four HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations, including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1.Some HDLS cases were misdiagnosed with unspecified psychiatric diagnoses in affected relatives from the original 1984 publication. However, HDLS is an encephalopathy dominated by a frontal lobe syndrome with an inexorably progressive and fatal course, where the different symptomatology in two recent cases confirmed the existence of acute and chronic variants.