A second generation synthesis of the MBr1 (globo-H) breast tumor antigen: new application of the n-pentenyl glycoside method for achieving complex carbohydrate protein linkages.
A new synthesis of the hexasaccharide MBr1 antigen (globo-H) is reported. A revised construction with improved efficiency was necessary because an anti-cancer vaccine containing this antigen is entering phase II and phase III clinical trials for prostate cancer. The key feature of this second generation synthesis is the preparation of globo-H as its n-pentenyl glycoside. This group serves as an anomeric protecting group and as a linker for bioconjugation to carrier protein. The resultant synthesis allows for the production of suitable quantities of globo-H for clinical trials.
Allen
J R
JR
Laboratory of Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
Allen
J G
JG
Zhang
X F
XF
Williams
L J
LJ
Zatorski
A
A
Ragupathi
G
G
Livingston
P O
PO
Danishefsky
S J
SJ
D000951:Antigens, Neoplasm / Q000737:chemistry*; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008969:Molecular Sequence Data; D013057:Spectrum Analysis
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines