Synthesis of Selected LeY and KH-1 Analogues: A Medicinal Chemistry Approach to Vaccine Optimization

As part of our ongoing anticancer vaccine program, we recently found that antibodies generated in response to the KH-1−KLH construct recognized not only KH-1 antigen but also the Lewis Y (Ley) antigen as well, with antibody titer levels much higher than those observed after immunization with individual Ley−KLH vaccine constructs. In an attempt to explore the structure-antigenic relationship of these carbohydrate epitopes, several analogues of both KH-1 and Ley were synthesized. A convergent synthetic approach to the analogues was designed on the basis of well-established glycal methodology, employing a minimum number of building blocks to generate competent antigens with high stereoselectivity and reasonable yield.