Biologics Through Chemistry: Total Synthesis of a Proposed Dual-acting Vaccine Targeting Ovarian Cancer by Orchestration of Oligosaccharide and Polypeptide Domains

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Mar 4

PMID 19253940

Citations 16

Authors

Jianglong Zhu

Qian Wan

Govind Ragupathi

Constantine M George

Philip O Livingston

Samuel J Danishefsky

Affiliations

Soon will be listed here.

Abstract

Carbohydrate and peptide-based antitumor vaccine constructs featuring clusters of both tumor associated carbohydrate antigens and mucin-like peptide epitopes have been designed, synthesized, and studied. The mucin-based epitopes are included to act, potentially, as T-cell epitopes in order to provoke a strong immune response. Hopefully the vaccine will simulate cell surface architecture, thereby provoking levels of immunity against cancer cell types displaying such characteristics. With this central idea in mind, we designed a new vaccine type against ovarian cancer. Following advances in glycohistology, our design is based on clusters of Gb(3) antigen and also incorporates a MUC5AC peptide epitope. The vaccine is among the most complex targeted constructs to be assembled by chemical synthesis to date. The strategy for the synthesis employed a Gb(3)-MUC5AC thioester cassette as a key building block. Syntheses of both nonconjugate and KLH-conjugated vaccines constructs have been accomplished.

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