Automated glycan assembly of Streptococcus pneumoniae type 14 capsular polysaccharide fragments

Abstract

A streamlined automated synthesis for S. pneumoniae type 14 and Group B Streptococcus type III capsular oligosaccharides with only one set of three building blocks is presented. Competitive ELISA provides some insight into minimal epitope.

Recyclable fluorous-tag assisted two-directional oligosaccharide synthesis enabled by interrupted Pummerer reaction mediated glycosylation

“…As a nal endeavor to demonstrate the utilization potential of the protocol, structurally more complex S. pneumonia type 14 (ST14) tetrasaccharide and octasaccharide were chosen as synthetic targets (Scheme 4). 39,40 The tetrasaccharide repeating unit is the smallest structure to induce ST14-specic antibody effects 41,42 and represents an important component for the development of synthetic or semi-synthetic pneumococcal vaccines. 43 Savage 44 and Seeberger 42,45 have developed glycoconjugate vaccine candidates, which are advantageous to clinically used vaccines on the basis of solution-phase synthesized tetrasaccharide fragments.…”

Synthetic Analogs of Streptococcus pneumoniae Capsular Polysaccharides and Immunogenic Activities of Glycoconjugates

“…Modern methods allow automated screening of carbohydrate ligands using on-chip carbohydrate arrays [54,59,62] and other carriers [139][140][141][142][143][144][145] to study epitope specificity of the tested antibodies. New efficient methods for synthesis of the most complex types of oligosaccharides have also been developed (see, for example, [146][147][148][149]), including the automated synthesis of oligosaccharides [150,151], which significantly simplifies preparation of extended libraries of the carbohydrate ligands.…”

Automated Chemical Solid‐Phase Synthesis of Glycans

“…AGA of bacterial antigens such as the capsular polysaccharides (CPSs) of Streptococcus pneumonia serotype 3 (ST3), serotype 8 (ST8), and serotype 14 (ST14) serves as a rapid and reliable method for accelerating the development of glycoconjugate vaccines. [ 61‐63 ] As exemplified by the automated synthesis of the CPS antigens of ST8, a combination of the building blocks 53 — 58 and the photolabile linker 7 was devised to produce all four tetrasaccharide frameshifts 59 — 62 of ST8 CPS after photo‐induced cleavage from the solid support and removal of the protecting groups (Scheme 11). [ 62 ] These conjugation‐ready tetrasaccharide frameshifts could then be screened in glycan microarray to identify the glycan epitope for the generation of efficacious vaccines.…”