Synthesis of octa- and dodecamers of d-ribitol-1-phosphate and their protein conjugates

The bacterial cell-wall-associated teichoic acids contain predominantly d-ribitol residues interconnected by phosphodiester linkages. Because of their location, these antigens may be vaccine candidates as part of conjugate vaccines. Here, we describe the synthesis of extended oligomers of d-ribitol-1-phosphate linked to a spacer having an amino group at its terminus. The synthesis utilized a fully protected d-ribitol-phosphoramidite that was oligomerized in a stepwise fashion followed by deprotection. The free oligomers were connected to bovine serum albumin using oxime chemistry. Thus, the ribitol phosphate oligomers were converted into keto derivatives, and the albumin counterpart was decorated with aminooxy groups. Reaction of the functionalized saccharide and protein moieties afforded conjugates having up to 20 ribitol phosphate chains.