Pursuit of optimal carbohydrate-based anticancer vaccines: preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewis(y) antigens.
A novel preparation of nonnatural glycoamino acids starting from n-pentenyl glycosides is described. The approach involves a Horner-Emmons olefination with a suitably protected glycine-derived phosphonate, followed by catalytic asymmetric hydrogenation, which proceeds with excellent diastereomeric selectivity. The synthetic methodology was useful for the preparation of glycoamino acids containing the Tn antigen, the MBr1 antigen (Globo-H), the Le(y) antigen, and lactose. These glycoamino acids can also serve as units for peptide synthesis. The synthesis of polyvalent glycopeptides containing three different antitumor antigens is described (28 and 29), and these have been prepared for conjugation to carrier protein in order to access the immunogenicity for tumor immunotherapy applications.
Allen
J R
JR
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Harris
C R
CR
Danishefsky
S J
SJ
D000606:Amino Sugars / Q000138:chemical synthesis*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006001:Glycoconjugates / Q000138:chemical synthesis*; D006020:Glycopeptides / Q000138:chemical synthesis*; D007167:Immunotherapy / Q000379:methods; D007983:Lewis Blood Group Antigens / Q000737:chemistry*; D011134:Polysaccharides / Q000138:chemical synthesis*; D018074:Vaccines, Conjugate / Q000737:chemistry*
D000606:Amino Sugars; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006001:Glycoconjugates; D006020:Glycopeptides; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D011134:Polysaccharides; C040286:Tn antigen; D018074:Vaccines, Conjugate; C119370:globo H-keyhole limpet hemocyanin QS-21 vaccine