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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.

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

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.

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 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.

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.