Open AccessDesign, Synthesis, and Preliminary Immunological Studies of MUC1-Based Antitumor Vaccines Adjuvanted with R- and S-FSL-1
Author(s) -
Yonghui Liu,
Bocheng Yan,
Zhaoyu Wang,
Haomiao Zhu,
Xiaona Yin,
Kun Wang,
Menglei Wang,
Wei Zhao
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00579
Subject(s) - adjuvant , lipopeptide , medicine , pharmacology , combinatorial chemistry , stereochemistry , chemistry , immunology , biology , genetics , bacteria
Fibroblast stimulating lipopeptide 1 (FSL-1) is the ligand of TLR2 and TLR6 and can be used as the vaccine adjuvant to prepare antitumor vaccines. However, FSL-1 is a stereoisomeric mixture that contains the R stereoisomer and S stereoisomer, and it is still unclear which stereoisomer has better adjuvant activities. In this work, we designed and synthesized MUC1-based antitumor vaccines adjuvanted with the stereoisomers R -FSL-1 and S -FSL-1, which were synthesized from the stereoisomeric building blocks R -Fmoc-Pam 2 Cys-OH and S -Fmoc-Pam 2 Cys-OH, respectively. Immunological evaluation indicated that both R -FSL-1 and S -FSL-1 can be used as adjuvants for the construction of MUC1-based antitumor vaccines, with R -FSL-1 showing a better adjuvant effect than S -FSL-1.