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.