Synthesis of Lewis Y Analogs and Their Protein Conjugates for Structure-Immunogenicity Relationship Studies of Lewis Y Antigen

Analogs of cancer-associated Lewis Y (Ley) antigen with varying structures at the reducing end were synthesized by a highly efficient strategy involving one-pot preactivation-based iterative glycosylation to obtain the key tetra-/pentasaccharide intermediates, which was followed by stereoselective fucosylation. After global deprotection, these oligosaccharides were coupled with carrier protein keyhole limpet hemocyanin. The resultant glycan-protein conjugates were subjected to immunological studies in mice. It was disclosed that the conjugate of the pentasaccharide analog of Lewis Y antigen was more immunogenic than that of the hexasaccharide analog but the antisera of both conjugates could indiscriminately recognize each carbohydrate hapten. These results suggested that the short Lewis Y analog may be utilized to develop functional conjugate cancer vaccines. More importantly, the results also proved that the reducing end glucose residue in the hexasaccharide analog of Lewis Y was probably not be involved...