One-Pot Methods for the Protection and Assembly of Sugars

In recent years, there has been rapid expansion of glycan synthesis, fueled by the recognition that the structural complexity of sugars translates to a myriad of biological functions. Such chemical syntheses involve many challenges, mostly due to the regio- and stereochemical aspects of glycosidic bond formation. One-pot strategies were developed to assist in attaining faster and more economical access to the glycan constructs. In this front, achievements in protecting group manipulation, glycosylation, and combinations of these have been reported. Protecting group manipulations in one pot take advantage of the reaction compatibility of commonly used transformations, many of which occur in high regioselectivity. Sequential glycosylations, on the other hand, rely on leaving group orthogonalities and reactivity tuning, as well as the preactivation technique. Altogether, these approaches offer attractive means to the much needed glycan structures and, consequently, help usher in advances in glycoscience.     

Analysis of a homologous series of non-reducing oligosaccharides from Arnica montana L. Roots

The oligosaccharide component compositions of a series of non-reducing oligosaccharides extracted from the roots of Arnica montana L. has been determined by gel permeation chromatography (g.p.c.). The range of oligosaccharides present was found to extend beyond the octasaccharide previously reported. with 16% to 19% of the oligosaccharides having a degree of polymerisation of between 11 and 19 and almost 3% having a degree of polymerisation greater than 20. The chromatographic behaviour of this series of oligosaccharides is compared with that observed for series of D-gluco-oligosaccharides.     

Variation among and within mountain birch trees in foliage phenols,carbohydrates, and amino acids,and in growth ofEpirrita autumnata larvae

Leaf quality of the mountain birch (Betula pubescens ssp.tortuosa) for herbivores was studied at several hierarchical levels: among trees, among ramets within trees, among branches within ramets, and among short shoots within branches. The experimental units at each level were chosen randomly. The indices of leaf quality were the growth rate of the larvae of a geometrid,Epirrita autumnata, and certain biochemical traits of the leaves (total phenolics and individual phenolic compounds, total carbohydrates and individual sugars, free and protein-bound amino acids). We also discuss relationships between larval growth rate and biochemical foliage traits. Larval growth rates during two successive years correlated positively at the level of tree, the ramet, and the branch, indicating that the relationships in leaf quality remained constant between seasons both among and within trees. The distribution of variation at different hierarchical levels depended on the trait in question. In the case of larval growth rate, ramets and short shoots accounted for most of the explained variation. In the case of biochemical compounds, trees accounted for most of the variance in the content of total phenolics and individual low-molecular-weight phenolics. In the content of carbohydrates (total carbohydrates, starch, fructose, glucose, and sucrose) and amino acids, variation among branches was generally larger than variation among trees. Variation among ramets was low for most compounds. No single leaf trait played a paramount role in larval growth. Secondary compounds, represented by phenolic compounds, or primary metabolites, particularly sugars, may both be important in determining the suitability of birch leaves for larvae. If phenols are causally more important, genet-specific analyses of foliage chemistry are needed. If sugars are of primary importance, within-genet sampling and analysis of foliage chemistry are necessary.     

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2009–2010

This review is the sixth update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2010. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, arrays and fragmentation are covered in the first part of the review and applications to various structural typed constitutes the remainder. The main groups of compound that are discussed in this section are oligo and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Many of these applications are presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 34: 268–422, 2015.

     

Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody–Drug Conjugation Chemistry

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.     

Synthesis and Evaluation of Glycoconjugates Comprising N‐Acyl‐Modified Thomsen–Friedenreich Antigens as Anticancer Vaccines

Thomsen–Friedenreich (TF) antigen is an important tumor‐associated carbohydrate antigen. Its low immunogenicity, however, limits its application in the development of anticancer vaccines. To solve this problem, several N‐acyl‐modified TF derivatives were synthesized and conjugated with carrier protein CRM197 (a mutated diphtheria toxoid cross‐reactive material). The immunological results in BALB/c mice demonstrated that these modified TF antigen conjugates could stimulate the production of higher titers of IgG antibodies that cross‐reacted with native TF antigen. These glycoconjugates showed strong lymphocyte proliferative response, suggesting that they can induce cellular immunity. Furthermore, the elicited antisera reacted strongly with TF‐positive tumor cells (4T1). In particular, the N‐monofluoroacetyl‐modified TF conjugate 4 ‐CRM197 showed the strongest complement‐dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.     

Determination of total dietary fibre and available carbohydrates: A rapid integrated procedure that simulates in vivo digestion

The new definition of dietary fibre introduced by Codex Alimentarius in 2008 includes resistant starch and the option to include non‐digestible oligosaccharides. Implementation of this definition required new methodology. An integrated total dietary fibre method was evaluated and accepted by AOAC International and AACC International (AOAC Methods 2009.01 and 2011.25; AACC Method 32–45.01 and 32–50.01, and recently adopted by Codex Alimentarius as a Type I Method. However, in application of the method to a diverse range of food samples and particularly food ingredients, some limitations have been identified. One of the ongoing criticisms of this method was that the time of incubation with pancreatic α‐amylase/amyloglucosidase mixture was 16 h, whereas the time for food to transit through the human small intestine was likely to be approximately 4 h. In the current work, we use an incubation time of 4 h, and have evaluated incubation conditions that yield resistant starch and dietary values in line with ileostomy results within this time frame. Problems associated with production, hydrolysis and chromatography of various oligosaccharides have been addressed resulting in a more rapid procedure that is directly applicable to all foods and food ingredients currently available.