Dissecting the Essential Role of Anomeric β-Triflates in Glycosylation Reactions

Glycosylations promoted by reagent triflate produce synthetic methods for the construction of scaffolding glycosidic spacious and glycoconjugates interests of biology and chemistry.

The process is expected to continue with the participation of a large number of high-energy activated intermediates such as triflates α- and β-glycosylation, or even more unstable glycosyl oxocarbenium-like species, of which only α-glycosyl triflates have been well characterized under reaction conditions representative. Interestingly, the remaining intermediates are less accessible, experimental yet described, seems to be very relevant in the α-selective process, which involves the weak acceptor.

Here, we report a detailed analysis of some paradigmatic examples and illustrations of the reaction, using a combination of chemicals, NMR, kinetic and theoretical approaches, which culminated in the unprecedented detection and quantification really β-glycosyl triflate intermediates in the mix of donor activated. This achievement is further used as a springboard for the characterization of the dynamics of triflate anomerization, which along with the substitution of the acceptor, adjust the stereochemical outcome of the reaction.

The data obtained convincingly show that, even for the reactions were very dissociative involving β-close ion pair (β-CIP) species, the formation of α-glycosides are of course preceded by a bimolecular α → β triflate interconversion, which under certain circumstances be level-step limit. Overall, our results rule out the prevalence of Curtin-Hammett rapid exchange assumption for most glycosylations and highlights the different reactivity properties of α- and β-glycosyl triflates to neutral acceptor and anion.

Dissecting the Essential Role of Anomeric β-Triflates in Glycosylation Reactions
Dissecting the Essential Role of Anomeric β-Triflates in Glycosylation Reactions

Click chemistry compared with thiols chemistry for the synthesis of site-selective glycoconjugate vaccine use as a carrier protein CRM 197

Conjugation chemistry is one of the main parameters affecting the immunogenicity of the vaccine glycoconjugate and rational approach towards a deeper understanding of their mechanisms of action will benefit from a very clear structure and well-marked. Here, different conjugation methods were investigated with the aim of controlling the glycosylation site and the density of the carrier protein glycosylation.

S. Typhimurium lipopolysaccharide O-antigen and the carrier protein CRM197 is used as a model. In particular, thiols and click chemistry is checked, both involving the linkage of the terminal reducing sugar units of O-antigen chain of different amino acids in the protein carrier. Thiol chemistry O-antigen conjugate is allowed only when the carrier protein is activated on the lysines and the relatively high number of linker, while the click chemistry allowed conjugate generation even when only one position on the protein activated and sites for both lysine and tyrosine.

Study Highlights click chemistry as a leading approach to the synthesis of glycoconjugates defined, useful to investigate the relationship between design conjugates and immune response. Schistosoma mansoni worms such as the release of excretion / secretory (E / S) products which modulate host immunity to allow infection. extracellular vesicles (EV) between this E / S products, yet the molecular mechanisms and function of S. mansoni EV interaction with the host immune cells is unknown.

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Here we show that EVs are released by S. mansoni schistosomula internalized by monocyte-derived human dendritic cells (moDCs). Importantly, we show that the uptake is mainly mediated by DC-SIGN (CD209). Blocking DC-SIGN is almost completely canceled EV uptake, while blocking the mannose receptor (MR, CD206) or dendritic cell immunoreceptor (DCIR, CLEC4A) had no effect on EV uptake.