Spassova Maria K, Bornmann William G, Ragupathi Govindaswami, Sukenick George, Livingston Philip O, Danishefsky Samuel J
Organic Synthesis Core Facility, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Org Chem. 2005 Apr 29;70(9):3383-95. doi: 10.1021/jo048016l.
[structure: see text] 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 (Le(y)) antigen as well, with antibody titer levels much higher than those observed after immunization with individual Le(y)-KLH vaccine constructs. In an attempt to explore the structure-antigenic relationship of these carbohydrate epitopes, several analogues of both KH-1 and Le(y) 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.
[结构：见正文]作为我们正在进行的抗癌疫苗项目的一部分，我们最近发现，针对KH-1-KLH构建体产生的抗体不仅能识别KH-1抗原，还能识别Lewis Y（Le(y)）抗原，且抗体滴度水平远高于用单个Le(y)-KLH疫苗构建体免疫后观察到的水平。为了探索这些碳水化合物表位的结构-抗原关系，合成了几种KH-1和Le(y)的类似物。基于成熟的糖烯方法设计了一种用于合成类似物的汇聚合成方法，使用最少数量的构建模块以高立体选择性和合理产率生成有效的抗原。
