A new model for the presentation of tumor-associated antigens and the quest for an anticancer vaccine: a solution to the synthesis challenge via ring-closing metathesis.
Fully synthetic, carbohydrate-based antitumor vaccine candidates have been synthesized in highly clustered modes. Multiple copies of tumor-associated carbohydrate antigens, Tn and STn, were assembled on a single cyclic peptide scaffold in a highly convergent manner. Ring-closing metathesis-mediated incorporation of an internal cross-linker was also demonstrated. In particular, this rigidified cross-linked construct would enhance a cluster-recognizing antibody response by retaining an appropriate distance between glycans attached to the peptide platform. Details of the design and synthesis of highly clustered antigens are described herein.
Jeon
Insik
I
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
Lee
Dongjoo
D
Krauss
Isaac J
IJ
Danishefsky
Samuel J
SJ
D000917:Antibody Formation; D017951:Antigen Presentation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology*; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000276:immunology*; D006020:Glycopeptides / Q000138:chemical synthesis / Q000276:immunology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; D010456:Peptides, Cyclic