Hydrogen-bonding cooperativity: using an intramolecular hydrogen bond to design a carbohydrate derivative with a cooperative hydrogen-bond donor centre

Neighbouring groups can be strategically located to polarise HO.OH intramolecular hydrogen bonds in an intended direction. A group with a unique hydrogen-bond donor or acceptor character, located at hydrogen-bonding distance to a particular OH group, has been used to initiate the hydrogen-bond network and to polarise a HO.OH hydrogen bond in a predicted direction. This enhanced the donor character of a particular OH group and made it a cooperative hydrogen-bond centre. We have proved that a five-membered-ring intramolecular hydrogen bond established between an amide NH group and a hydroxy group (1,2-e,a), which is additionally located in a 1,3-cis-diaxial relationship to a second hydroxy group, can be used to select a unique direction on the six-membered-ring intramolecular hydrogen bond between the two axial OH groups, so that one of them behaves as an efficient cooperative donor. Talose derivative 3 was designed and synthesised to prove this hydrogen-bonding network by NMR spectroscopy, and the mannopyranoside derivatives 1 and 2 were used as models to demonstrate the presence in solution of the 1,2-(e,a)/five-membered-ring intramolecular hydrogen bond. Once a well-defined hydrogen-bond is formed between the OH and the amido groups of a pyranose ring, these hydrogen-bonding groups no longer act as independent hydrogen-bonding centres, but as hydrogen-bonding arrays. This introduces a new perspective on the properties of carbohydrate OH groups and it is important for the de novo design of molecular recognition processes, at least in nonpolar media. Carbohydrates 1-3 have shown to be efficient phosphate binders in nonpolar solvents owing to the presence of cooperative hydroxy centres in the molecule.     

Reversible conformational transitions of a polymer brush containing boronic acid and its interaction with mucin glycoprotein

Reversible changes of the height of a polymer brush containing phenylboronic acid were studied. The polymer brush thickness underwent reversible changes of 0.5–1 nm, in response to the changes in composition of the contacting aqueous phase from deionized water to bicarbonate buffer and vice versa, apparently due to the conformational transition of the weak polyelectrolyte to the more extended electrically charged state. Adsorption of mucin glycoprotein to the polymer brush took place due to boronate/sugar interactions between the glycoprotein and the graft copolymer and resulted in further increase of the brush height by ca. 1.5 nm, as observed by means of spectral correlation spectroscopy and ellipsometry.

     

Synthesis of Peptidoglycan Fragments from Enterococcus faecalis with Fmoc‐Strategy for Glycan Elongation

Peptidoglycan (PGN) is an essential structural component of the bacterial cell wall conferring cell shape, which can be recognized by host‐recognition proteins and receptors as well as bacterial surface proteins. In this work, the PGN partial structures from Enterococcus faecalis that contain a tetrasaccharide and an octasaccharide with a unique heptapeptide were synthesized via an Fmoc‐strategy for elongation of the glycan chains. Namely, a 4′‐O ‐Fmoc‐protected disaccharide was utilized as the key intermediate in this efficient synthetic pathway for preparing various PGN fragments. Both the tetrasaccharide and octasaccharide with the unique heptapeptide were successfully synthesized for the first time.     

Substrate-independent transduction of chromophore-free organic and biomolecular transformations into color

The concept of synthetic multifunctional pores as substrate-independent optical signal transducers of chemical reactions is introduced with emphasis on the combination with substrate-specific signal generation in biomolecular transformations. Comparison with the general electrochemical transduction, known from conventional biosensors, and the general optical transduction of analyte-specific biomolecular recognition (rather than transformation), known from immunosensing, reveals the fundamental nature of the concept as well as an attractive complementarity to existing methods. Examples with transferases, hydrolases, lyases, and even an isomerase demonstrate that optical transduction with synthetic multifunctional pores is general far beyond the substrate-specific signal generators of electrochemical transduction, that is, the oxidoreductases, and absolutely unproblematic. In part very recent breakthroughs are used to highlight the remarkable promise of synthetic multifunctional pores as optical transducers of biomolecular transformation with regard to practical sensing and screening applications.     

Meeting the sustainable development goals in a tropical climate

This article reflects on the Federation of Asian Chemical Societies (FACS) Citation Award Lecture delivered in the Industrial Technology Research Institute Symposium on CO₂ Utilization and Green Technology during the 18th Asian Chemical Congress held in Taipei, December 12, 2019. Malaysia produces sizable amounts of palm oil and palm kernel oil, with palm fronds and tree trunks as the main waste. At the Malaysia Japan International Institute of Technology, the biomass was decomposed to produce fine chemicals, used as substrate for mushroom growth, and converted to bio-coke for heat energy. A notable difference has been found regarding the emission of greenhouse gases from a natural peat forest and those from the oil palm plantation converted from peatlands, where in the palm plantation, water table is lowered and aerobic processes occurs, resulting in more CO₂ being released compared to CH₄. The introduction of fertilizers to the plantation resulted in more N₂O being released. The team has also pioneered a project to plant temperate vegetables. Cooling pipes (16–18°C with circulating water cooled by chiller) were embedded within each thermal conditioning soil plot. Lettuce and radish, the experimental plants, showed good growth in the thermal conditioning soil due to nitrogen-fixing bacteria, which were destroyed at a higher temperature.     

Platform Synthetic Lectins for Divalent Carbohydrate Recognition in Water

Biomimetic carbohydrate receptors (“synthetic lectins”) have potential as agents for biological research and medicine. However, although effective strategies are available for “all‐equatorial” carbohydrates (glucose, etc.), the recognition of other types of saccharide under natural (aqueous) conditions is less well developed. Herein we report a new approach based on a pyrene platform with polar arches extending from aryl substituents. The receptors are compatible with axially substituted carbohydrates, and also feature two identical binding sites, thus mimicking the multivalency observed for natural lectins. A variant with negative charges forms 1:2 host/guest complexes with aminosugars, with K₁>3000 m ^?1 for axially substituted mannosamine, whereas a positively charged version binds the important α‐sialyl unit with K₁≈1300 m ^?1.     

Prompt chemoenzymatic synthesis of diverse complex-type oligosaccharides and its application to the solid-phase synthesis of a glycopeptide with Asn-linked sialyl-undeca- and asialo-nonasaccharides

We describe herein the preparation of 24 pure asparagine-linked oligosaccharides (Asn-oligosaccharides) from asparagine-linked biantennary complex-type sialylundecasaccharide [(NeuAc-alpha-2,6-Gal-beta-1,4-GlcNAc-beta-1,2-Man-alpha-1,6/1,3-)(2)-Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-asparagine, 2] obtained from egg yolk. Our synthetic strategy aimed at adapting branch specific exo-glycosidases digestion (beta-D-galactosidase, N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase) of the individual asialo-branch after preparation of monosialyloligosaccharides obtained from 2 by acid hydrolysis of NeuAc. In order to perform branch specific exo-glycosidase digestion, isolation of pure monosialyloligosaccharides obtained was essential. However, isolation of two kinds of monosialyloligosaccharides are difficult by HPLC due to their highly hydrophilic nature. Therefore, we examined chemical protection with hydrophobic protecting (Fmoc and benzyl) groups. These chemical protection enabled us to separate the monosialyloligosaccharides by use of a HPLC column (ODS) on synthetic scales. Using these pure monosialiloligosaccharides enable us to obtain 24 Asn-linked oligosaccharides (100 mg scale) within a few weeks by branch specific exo-glycosidase digestions (alpha-D-neuraminidase, beta-D-galactosidase, N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase). In addition, solid-phase synthesis of glycopeptide having Asn-linked sialyl-undeca- and asialo-nonasaccharides thus obtained, was also performed on an acid labile HMPA-PEGA resin.     

Affinity Enhancement by Dendritic Side Chains in Synthetic Carbohydrate Receptors

Dendritic side chains have been used to modify the binding environment in anthracene‐based synthetic carbohydrate receptors. Control of length, charge, and branching enabled the positioning of side‐chain carboxylate groups in such a way that they assisted in binding substrates rather than blocking the cavity. Conformational degeneracy in the dendrimers resulted in effective preorganization despite the flexibility of the system. Strong binding was observed to glucosammonium ions in water, with K_a values up to 7000 M ^?1. Affinities for uncharged substrates (glucose and N‐acetylglucosamine) were also enhanced, despite competition from solvent and the absence of electrostatic interactions.     

Combinatorial synthesis of an oligosaccharide library by using beta-bromoglycoside-mediated iterative glycosylation of selenoglycosides: rapid expansion of molecular diversity with simple building blocks

A new method for constructing an oligosaccharide library composed of structurally defined oligosaccharides is presented based on an iterative glycosylation of selenoglycosides. Treatment of 2-acyl-protected selenoglycosides with bromine selectively generates beta-bromoglycosides, which serve as glycosyl cation equivalents in the oligosaccharide synthesis. Thus, the coupling of the bromoglycosides with another selenoglycoside affords the corresponding glycosylated selenoglycosides, which can be directly used to next glycosylation. The iteration of this sequence allows the synthesis of a variety of oligosaccharides including an elicitor active heptasaccharide. A characteristic feature of the iterative glycosylation is that glycosyl donors and acceptors with the same anomeric reactivity can be selectively coupled by activation of the glycosyl donor prior to coupling with the glycosyl acceptor. Therefore, same selenoglycosides can be used for both the glycosyl donors and the acceptors. This feature has been exemplified by a construction of an oligosaccharide library directed to elicitor-active oligosaccharides. The library composed of stereochemically defined oligoglucosides with considerable structural diversity can be constructed starting from simple selenoglycosides.     

Probing bacterial-toxin inhibition with synthetic glycopolymers prepared by tandem post-polymerization modification: role of linker length and carbohydrate density

Probing the depths: A tandem post-polymerization modification strategy was used to systematically probe the multivalent inhibition of a bacterial toxin as a function of linker length (see scheme), carbohydrate density, and glycopolymer chain length. Guided by structural-biology information, the binding-pocket depth of the toxin was probed and used as a means to specifically improve inhibition of the toxin by the glycopolymer.     

Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K_a≈20 000 m ^?1, whereas the other one binds an O‐GlcNAcylated peptide with K_a≈70 000 m ^?1. These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts.     

A Carbohydrate–Anion Recognition System in Aprotic Solvents

A carbohydrate–anion recognition system in nonpolar solvents is reported, in which complexes form at the B‐faces of β‐D ‐pyranosides with H1‐, H3‐, and H5‐cis patterns similar to carbohydrate–π interactions. The complexation effect was evaluated for a range of carbohydrate structures; it resulted in either 1:1 carbohydrate–anion complexes, or 1:2 complex formation depending on the protection pattern of the carbohydrate. The interaction was also evaluated with different anions and solvents. In both cases it resulted in significant binding differences. The results indicate that complexation originates from van der Waals interactions or weak CH ??? A^? hydrogen bonds between the binding partners and is related to electron‐withdrawing groups of the carbohydrates as well as increased hydrogen‐bond‐accepting capability of the anions.     

Highly effective acyclic carbohydrate receptors consisting of aminopyridine, imidazole, and indole recognition units

Neutral imidazole/aminopyridine- and indole/aminopyridine-based receptors, 1 and 2, have been established as highly effective and selective carbohydrate receptors. These receptors effectively recognise neutral carbohydrates through multiple interactions, including neutral hydrogen bonds and CH...pi interactions between the sugar CH groups and the aromatic rings of the receptors. The design of these receptors was inspired by the binding motifs observed in the crystal structures of protein-carbohydrate complexes. The formation of very strong complexes with beta-glucopyranoside 5, beta-maltoside 8, and alpha-maltoside 9 in organic media has been characterised by 1H NMR spectroscopy and confirmed by a second, independent technique, namely fluorescence spectroscopy. The syntheses, molecular-modelling studies, binding properties of the receptors 1 and 2 toward selected mono- and disaccharides as well as comparative binding studies with receptors 3 and 4 are described.