Anomeric O-Functionalization of Carbohydrates for Chemical Conjugation to Vaccine Constructs

Abstract

Carbohydrates mediate a wide range of biological interactions, and understanding these processes benefits the development of new therapeutics. Isolating sufficient quantities of glycoconjugates from biological samples remains a significant challenge. With advances in chemical and enzymatic carbohydrate synthesis, the availability of complex carbohydrates is increasing and developing methods for stereoselective conjugation these polar head groups to proteins and lipids is critically important for pharmaceutical applications. The aim of this review is to provide an overview of commonly employed strategies for installing a functionalized linker at the anomeric position as well as examples of further transformations that have successfully led to glycoconjugation to vaccine constructs for biological evaluation as carbohydrate-based therapeutics.

Carrier diversity and chemical ligations in the toolbox for designing tumor-associated carbohydrate antigens (TACAs) as synthetic vaccine candidates

“…62 In this regard, the excellent review originating from Gervay-Hague's group has covered the essential elements of the glycome syntheses. 63 The paradigm of skills in the art of oligosaccharide syntheses involved: (1) strategy (chemical and/ or enzymatic); (2) anomeric stereocontrol;…”

“…As will be seen throughout this review, several intermediates described have been applied toward the syntheses of TACA vaccines and the review by Gervay-Hague has already highlighted their usefulness in detailed analyses. 63 For instance, an obvious and ''old-fashion'' application of the alkene functionality has been its use in the reductive amination ligation of bacterial capsular polysaccharides to protein carriers after ozonolysis that generated an aldehyde. Several anti-bacterial vaccines relied on this approach.…”

“…was photoactivated at 365 nm in the presence of BSA/HSA to afford intermediate carbene 61 that provided vaccine 62 having, under the optimized conditions, B10 Tn residues per protein. In addition, they used a conventional amide coupling of an analogous carboxylic acid derivative (63) to compare the extent and variation of antibody levels Scheme 6 Roy's syntheses of the TF vaccines (56,57) and polymer (59) that did not contain mucin peptides. 101,102 Scheme 7 Chemical ligation of the diazirine-derived T N TACA (60) by photoaffinity labelling (PAL) and by amide coupling (63) to afford BSA vaccines (62,64).…”

Thiocarbonyl as a Switchable Relay-Auxiliary Group in Carbohydrate Synthesis

“…On consideration of the glycosylation reaction, 10 a glycosyl donor bearing a leaving group on the anomeric center is activated by the promoter to generate an oxocarbenium ion that is further intercepted by the hydroxyl group of the adjacent acceptor. A latent−active strategy and latent glycosylation were recently developed to link several building blocks together to streamline oligosaccharide synthesis.…”

“…On consideration of the glycosylation reaction, a glycosyl donor bearing a leaving group on the anomeric center is activated by the promoter to generate an oxocarbenium ion that is further intercepted by the hydroxyl group of the adjacent acceptor. A latent–active strategy and latent glycosylation were recently developed to link several building blocks together to streamline oligosaccharide synthesis. , The formation of a glycosidic linkage generates a new stereogenic center at the anomeric carbon ( C 1); therefore, the control of stereoselective glycosylation is one of the most challenging tasks and has long been a major bottleneck for carbohydrate chemistry.…”