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

J Am Chem Soc. 2009 Oct 14;131(40):14337-44. doi: 10.1021/ja9052625.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • Antigen Presentation
  • Antigens, Tumor-Associated, Carbohydrate / chemistry*
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Cancer Vaccines / chemical synthesis*
  • Cancer Vaccines / immunology*
  • Glycopeptides / chemical synthesis
  • Glycopeptides / immunology
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / immunology

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Cancer Vaccines
  • Glycopeptides
  • Peptides, Cyclic