Synthesis of a well-defined glycoconjugate vaccine by a tyrosine-selective conjugation strategy

Abstract

An anti-candidiasis glycoconjugate vaccine was prepared via a tyrosine-selective alkynylation and a click chemistry mediated glycoconjugation sequence. It features a well-defined glycan, protein carrier, and connectivity. The construct, although with significantly lower carbohydrate loading and a shorter b-(1,3) glucan chain than the well-established anti-candidiasis vaccine derived from the random conjugation of laminarin at lysines, elicited a comparable level of specific IgG antibodies.

Covalent protein modification: the current landscape of residue-specific electrophiles

“…However, this electrophile is specific to the sialic-acid scaffold, and is therefore not amenable as a general tool for profiling tyrosine reactivity. Promising candidates for global tyrosine labeling are cyclic diazodicarboxamides such as 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD; Figure 4d) [59,60], which functions via an ene-type reaction that is amenable to aqueous conditions.…”

18F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

“…For example, Hu and co-workers take advantage of the tyrosine-selective transformation to the synthesis of a well-defined conjugate anti-candidiasis vaccine glycosylated at tyrosines. [82] Ban et. al .…”

Chemical synthesis of the outer core oligosaccharide of Escherichia coli R3 and immunological evaluation

“…The development of LPS–based vaccines, therapeutics, and diagnostics requires well-defined oligosaccharides conjugated to carrier proteins for immunological studies to identify the structural motifs that can elicit protective antibody responses. 4c, 11 Although oligosaccharides can be isolated from bacteria, the homogeneity cannot be achieved due to the variations of natural oligosaccharides during the processes of isolation and conjugation to carriers. 12 Chemical synthesis of well-defined oligosaccharides can overcome this problem by utilizing an artificial linker at the reducing end that allows conjugation to carrier proteins.…”

“…12 Chemical synthesis of well-defined oligosaccharides can overcome this problem by utilizing an artificial linker at the reducing end that allows conjugation to carrier proteins. 11c, 13 Moreover, it can provide various sub–structures for structure–activity relationships study to determine the minimal epitope that can elicit protective immune response. 11b, 14 Herein, an all α–linked pentasaccharide of E. coli R3 outer core was chemically synthesized with a propyl amino linker at the reducing end (Figure 1B), and was conjugated to the nontoxic mutant of diphtheria toxin CRM 197 to afford a glycoprotein.…”

“…11c, 13 Moreover, it can provide various sub–structures for structure–activity relationships study to determine the minimal epitope that can elicit protective immune response. 11b, 14 Herein, an all α–linked pentasaccharide of E. coli R3 outer core was chemically synthesized with a propyl amino linker at the reducing end (Figure 1B), and was conjugated to the nontoxic mutant of diphtheria toxin CRM 197 to afford a glycoprotein. Furthermore, levels of IgG and IgM antibodies against the pentasaccharide and in vitro bactericidal activity of these antibodies against E. coli O157:H7 were evaluated.…”