The proposed progam is centered at the chemical synthesis of complex saccharides which can be effectively employed as immunogens. We are aiming at the synthesis of well defined carbohydrate units which have been reported to be a part of tumor associated glycoconjugates. For example, the glycolipid Ga1NAc Beta 1-3 Gal Alpha 1-3 Gal Beta 1-4 Glc Beta 1-ceramide has been found to be present in acute leukemia cells. Since the antigenicity of such glycoconjugates resides in the carbohydrate portion of the molecule, we hereby propose to develop a chemical synthesis of Ga1NAc Beta 1-3 Gal Alpha 1-3 Gal Beta 1-4 Glc Beta 1- OZ (Z = H or (CH2)8 COOCH3). Since the structure of the carbohydrate units of various tumor associated glycoconjugates have been clearly elucidated, we propose a synthetic approach for the procurement of such artificial antigens. Attention will be focussed on the synthesis of glycosides that possess an aglycon which can serve as a bridge for attachment to high molecular weight substances. Recent advances made in the synthesis of oligosaccharides and our established success in this area support the fact that synthesis of desired carbohydrate units can be accomplished. Availability of various glycosylating agents, new catalysts for O-glycoside formation and diverse protecting groups have proven to be the ladder of success toward the chemical synthesis of complex saccharides. The structures of our synthetic antigens will be established by n.m.r. studies, mass spectroscopy and various other methods. Out synthetic antigens prepared in a very pure form will be further utilized to raise their antibodies. The availability of an antigen moiety linked to a solid support will facilitate purification of the antibodies raised against the corresponding antigens. The purified antibodies can play an important role in various biochemical and immunological studies. Moreover, these antibodies have come to play an important role in the potential development of more specific chemotherapeutic agents. For the latter purposes, the antibodies may be combined with or preferably covalently linked to drugs routinely used in cancer chemotherapy.
