Defining the Molecular Recognition of Globo H (Human Breast Cancer) Antigen through Probe Structures Prepared by Total Synthesis

摘要

Recently, we have synthesized the MBrl antigen (1). As its name implies, this novel hexasaccharide, which is a human breast and ovarian cancer antigen, is recognized by the MBrl antibody. Furthermore, the MBrl antigen has been shown to be immunogenicin mice. All indications are that the fucose residue is critical for the recognition of antigen by antibody. For instance, the desfucosyl system SSEA-3 <2) fails to bind to MBrl antibody. It was of interest to ascertain whether truncated or isomeric versions of 1, which contain the critical fucose moiety, but Jack residues from the potential reducing end of the carbohydrate domain, would be recognized by MBrl antibody. Toward that end, we set as a goal the synthesis of truncated and atereoisomeric forms of the MBrl antigen which would deal with this question at a detailed level. In this paper we report the synthesis of four novel analogues of MBrl antigen (l) (Figure 1).