Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines. Issue 30 (6th July 2016)

• Record Type: Journal Article
• Authors: Xiao, An; Zheng, Xiu-Jing; Song, Chengcheng; Gui, Yue; Huo, Chang-Xin; Ye, Xin-Shan
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 30(2016)
• Page Start: 7226
• Page End: 7237
• Publication Date: 2016-07-06
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c6ob01092j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Unnatural STn disaccharides with N -acetyl modifications were incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptide–protein conjugates showed high immunogenicity. Abstract : Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N -acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccineV2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides.