Sialic acid recognition remains an interesting and challenging target in molecular receptor design. Herein, we report a series of benzoboroxole-based receptors in which cationic hydrogen-bond donors ...have been introduced and shown to promote multipoint sialic acid recognition. One striking feature revealed by these receptors is that the carboxylate sialic acid residue is the primary binding determinant for recognition by benzoboroxole, in which the presence of charge-reinforced hydrogen bonds results in enhanced selectivity for sialic acid over other carbohydrates and a 4.5-fold increase in affinity. These findings open up wide possibilities for benzoboroxole-based receptors use in life science research, biotechnology, and diagnostics.
Although the preparation of anomeric glycosylsulfonyl fluoride was unsuccessful, a tetra‐O‐acetylated C‐glucosylpropanesulfonyl fluoride was synthesized starting from the corresponding thioacetate ...via sulfonate formation as the key intermediate. This sulfonyl fluoride was a bench‐stable product that reacted promptly with primary and secondary alkylamines at 80 °C to give the corresponding sulfonamides in good yield. On the other hand, the same fluoride was inert toward arylamines whereas its precursor, the sulfonyl chloride, showed good reactivity. Another limitation of the acetylated sugar sulfonyl fluoride was its lack of reactivity with a multivalent aminated calixarene, this being due to acetyl transfer from the carbohydrate moiety to the amino groups of the scaffold. Fortunately, the tetra‐O‐benzylated C‐glucosylpropanesulfonyl fluoride, prepared by the same reaction sequence employed for the synthesis of the acetylated analogue, reacted with the tetra‐aminopropyl‐calix4arene to afford the corresponding sulfonamide‐linked sugar cluster in high isolated yield. A similar approach to the synthesis of calixarene‐based iminosugar clusters was unsuccessful because 1‐deoxynojirimycin sulfonyl fluoride derivatives could not be generated. However, a tetra‐propylsulfonyl fluoride calixarene, obtained from the free‐OH calix4arene through a three‐step reaction sequence, underwent clean coupling with both C‐glucosylpropylamine and N‐aminopentyl‐1‐deoxy‐deoxynojirimycin derivatives to give the corresponding tetravalent sugar and iminosugar clusters. This metal‐free click reaction may constitute a valuable tool in the arsenal of ligation tools for the synthesis of multivalent carbohydrate architectures.
The metal‐free coupling between a tetra‐aminated calixarene and a bench‐stable C‐glycosylsulfonyl fluoride gave the corresponding sugar cluster in good yield. The reversed sulfonamide bioisostere of the latter was prepared using a tetrasulfonyl fluoride calixarene and a C‐glycosylalkylamine.
A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions ...between mono- or trivalent azido-armed iminosugars and calix8arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ Ki being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix8arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.
Glycans - simple or complex carbohydrates - play key roles as recognition determinants and modulators of numerous physiological and pathological processes. Thus, many biotechnological, diagnostic and ...therapeutic opportunities abound for molecular recognition entities that can bind glycans with high selectivity and affinity. This review begins with an overview of the current biologically and synthetically derived glycan-binding scaffolds that include antibodies, lectins, aptamers and boronic acid-based entities. It is followed by a more detailed discussion on various aspects of their generation, structure and recognition properties. It serves as the basis for highlighting recent key developments and technical challenges that must be overcome in order to fully deal with the specific recognition of a highly diverse and complex range of glycan structures.
Development of natural and artificial receptors with high affinity and exquisite specificity for various purposes remains an important goal and challenge.
Recognition of oligosaccharides is associated with very limited specificity due to their strong solvation in water and the high degree of subtle structural variations between them. Here, ...oligosaccharide recognition sites are created on material surfaces with unmatched, binary on–off binding behavior, sharply discriminating a target oligosaccharide over closely related carbohydrate structures. The basis for the superselective binding behavior relies on the highly efficient generation of a pure, high order complex of the oligosaccharide target with synthetic carbohydrate receptor sites, in which the spatial arrangement of the multiple receptors in the complex is preserved upon material surface incorporation. The synthetic binding scaffolds can easily be tailored to recognize different oligosaccharides and glycoconjugates, opening up a realm of possibilities for their use in a wide field of applications, ranging from life sciences to diagnostics.
A unique modular, synthetic strategy allows for the creation of artificial binding sites with precise spatial positioning of multiple carbohydrate receptors, enabling the remarkable ability to distinguish a target oligosaccharide over closely related carbohydrate structures. The synthetic binding scaffolds can easily be tailored to bind not only specifically oligosaccharides in free form but also when they are linked to proteins as glycoconjugates.
Considering the new IPCC report and its recent suggestions, it is important to pay serious attention to the Urban Heat Island issue. In this study, satellite images acquired by the Worldview3 sensor ...(WV3) were processed to classify the different kinds of urban surface and to compute the albedo value for each surface.
Then several UHI mitigation scenarios were analyzed, varying selectively the surface albedo by choosing solar reflective materials. Clay tile pitched roofs, dark roofs and parking areas were considered as “modifiable surfaces” and their albedo values were increased on the basis of the literature and of data made available by product manufacturers.
For each proposed scenario, the reduction of intensity of the Urban Heat Island effect (ATD), the energy saving brought by lower absorption of air conditioning systems (ΔE) and the consequent cost savings were calculated. All the scenarios proved to be convenient and with a relatively fast return on investment. In particular, two scenarios involving the modification of several surfaces at the same time proved to be the most promising ones from the perspective of a public administration, with significant benefits on the well-being of the population, as well as with similar and relatively short payback periods.
•Urban Heat Island (UHI) is an important problem that exacerbates and aggravates the effects of global warming;•Remote Sensing data provide useful information for urban surfaces classification and characterization;•Solar reflective materials play an increasingly important role in the UHI mitigation by increasing surface albedo;•Replacing some types of urban surfaces with solar reflective material brings an advantage both for UHI mitigation and in economic terms.
The cover picture shows a stamp celebrating the 100th anniversary of the 1906 Nobel prize, won by the French chemist Henri Moissan for the isolation of fluorine. After its discovery, the fluorine ...atom became part of many organic reagents, and fluorination played a key role in organic synthesis, drug design, and polymeric‐material production. Recently, Sharpless and co‐workers highlighted sulfonyl fluorides as potential click reagents owing to their easy preparation and purification, high stability under basic conditions, and good reactivity towards C‐, O‐, and N‐nucleophiles (see Angew. Chem. Int. Ed. 2014, 126, 9620). In this context, stable sulfonyl fluorides featuring sugar, iminosugar, and calixarene moieties have been prepared and reacted with amines under metal‐free conditions to give monovalent and multivalent sulfonamide derivatives. Details are discussed in the article by A. Marra, A. Dondoni et al. on p. 5102 ff.
The ability to design surfaces with reversible, high-affinity protein binding sites represents a significant step forward in the advancement of analytical methods for diverse biochemical and ...biomedical applications. Herein, we report a dynamic supramolecular strategy to directly assemble proteins on surfaces based on multivalent host–guest interactions. The host–guest interactions are achieved by one-step nanofabrication of a well-oriented β-cyclodextrin host-derived self-assembled monolayer on gold (β-CD-SAM) that forms specific inclusion complexes with hydrophobic amino acids located on the surface of the protein. Cytochrome c, insulin, α-chymotrypsin, and RNase A are used as model guest proteins. Surface plasmon resonance and static time-of-flight secondary ion mass spectrometry studies demonstrate that all four proteins interact with the β-CD-SAM in a specific manner via the hydrophobic amino acids on the surface of the protein. The β-CD-SAMs bind the proteins with high nanomolar to single-digit micromolar dissociation constants (K D). Importantly, while the proteins can be captured with high affinity, their release from the surface can be achieved under very mild conditions. Our results expose the great advantages of using a supramolecular approach for controlling protein immobilization, in which the strategy described herein provides unprecedented opportunities to create advanced bioanalytic and biosensor technologies.
Correction for 'The challenges of glycan recognition with natural and artificial receptors' by Stefano Tommasone
et al.
,
Chem. Soc. Rev.
, 2019,
48
, 5488-5505.
Since glycoproteins have become increasingly recognized as key players in a wide variety of disease processes, there is an increasing need for advanced affinity materials for highly selective ...glycoprotein binding. Herein, for the first time, a surface-initiated controlled radical polymerization is integrated with supramolecular templating and molecular imprinting to yield highly reproducible synthetic recognition sites on surfaces with dissociation constants (K D) in the low micromolar range for target glycoproteins and minimal binding to nontarget glycoproteins. Importantly, it is shown that the synthetic strategy has a remarkable ability to distinguish the glycosylated and nonglycosylated forms of the same glycoprotein, with a >5-fold difference in binding affinity. The precise control over the polymer film thickness and positioning of multiple carbohydrate receptors plays a crucial role in achieving an enhanced affinity and selectivity. The generated functional materials of unprecedented glycoprotein recognition performance open up a wealth of opportunities in the biotechnological and biomedical fields.
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