Synthesis of selected LeY and KH-1 analogues: a medicinal chemistry approach to vaccine optimization.
[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.
Spassova
Maria K
MK
Organic Synthesis Core Facility, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Bornmann
William G
WG
Ragupathi
Govindaswami
G
Sukenick
George
G
Livingston
Philip O
PO
Danishefsky
Samuel J
SJ
D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D002240:Carbohydrate Sequence; D002626:Chemistry, Pharmaceutical / Q000379:methods; D007114:Immunization; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D009844:Oligosaccharides; D014614:Vaccines, Synthetic; C105737:antigen KH-1