基于MUC1的抗肿瘤疫苗与-和-FSL-1联合使用的设计、合成及初步免疫学研究。
Design, Synthesis, and Preliminary Immunological Studies of MUC1-Based Antitumor Vaccines Adjuvanted with - and -FSL-1.
作者信息
Liu Yonghui, Yan Bocheng, Wang Zhaoyu, Zhu Haomiao, Yin Xiaona, Wang Kun, Wang Menglei, Zhao Wei
机构信息
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Key Laboratory of Molecular Drug Research and KLMDASR of Tianjin, Nankai University, No. 38 Tongyan Road, Haihe Education Park, Tianjin 300353, P. R. China.
出版信息
ACS Med Chem Lett. 2020 Jun 22;11(7):1371-1376. doi: 10.1021/acsmedchemlett.9b00579. eCollection 2020 Jul 9.
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 stereoisomer and 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 -FSL-1 and -FSL-1, which were synthesized from the stereoisomeric building blocks -Fmoc-PamCys-OH and -Fmoc-PamCys-OH, respectively. Immunological evaluation indicated that both -FSL-1 and -FSL-1 can be used as adjuvants for the construction of MUC1-based antitumor vaccines, with -FSL-1 showing a better adjuvant effect than -FSL-1.
成纤维细胞刺激脂肽1（FSL-1）是Toll样受体2（TLR2）和Toll样受体6（TLR6）的配体，可作为疫苗佐剂用于制备抗肿瘤疫苗。然而，FSL-1是一种立体异构体混合物，包含立体异构体和立体异构体，目前仍不清楚哪种立体异构体具有更好的佐剂活性。在本研究中，我们设计并合成了基于粘蛋白1（MUC1）的抗肿瘤疫苗，分别用立体异构体-FSL-1和-FSL-1作为佐剂，它们分别由立体异构的构建模块-Fmoc-PamCys-OH和-Fmoc-PamCys-OH合成。免疫学评估表明，-FSL-1和-FSL-1均可作为构建基于MUC1的抗肿瘤疫苗的佐剂，其中-FSL-1的佐剂效果优于-FSL-1。
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