Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2022-09-13 , DOI: 10.1016/j.bmcl.2022.128986 Jun Liao 1 , Xiaobin Zhuo 2 , Bo Pan 3 , Yan Zou 2 , Xiaoyun Chai 2 , Qiuye Wu 2 , Shichong Yu 2 , Weihua Pan 3 , Qingjie Zhao 2
Herein, the di- and trisaccharide mimics of the hexasaccharide antigen related to Bacillus anthracis were synthesized and covalently coupled with carrier proteins, such as keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA), to form the corresponding glycoconjugates 1–6. 2,3,4,6-Tetra-O-benzyl thioglycoside and 2-deoxyl-2-phthalylamino-3,4,6-tri-O-benzyl thioglycoside were applied as glycosyl donors to guarantee α or β-configuration of the newly formed glycosidic bonds. Glutaraldehyde was used as a homobifunctional cross-linker for high-efficiency coupling. The synthetic KLH-glycoconjugates 2, 4 and 6 were also used to vaccinate female Balb/c mice and the preliminary results of ELISA uncovered that all three KLH-conjugates could induce immune responses and generate oligosaccharide-specific total IgG antibodies. The trisaccharide 8, the glycosyl part of glycoconjugate 4, is of great immunogenicity.
中文翻译:
炭疽杆菌相关二糖/三糖缀合物的合成和初步免疫学特性
在此,合成了与炭疽杆菌相关的六糖抗原的二糖和三糖模拟物,并与载体蛋白(例如匙孔血蓝蛋白(KLH)和牛血清白蛋白(BSA))共价偶联,形成相应的糖复合物1 – 6。2,3,4,6-四-O-苄基硫代糖苷和2-脱氧-2-邻苯二甲氨基-3,4,6-三-O-苄基硫代糖苷用作糖基供体,以保证新的α或β-构型形成糖苷键。戊二醛被用作同双功能交联剂以实现高效偶联。合成的KLH-糖缀合物2、4和6也用于对雌性Balb/c小鼠进行疫苗接种,ELISA的初步结果表明,所有三种KLH-缀合物都能诱导免疫反应并产生寡糖特异性总IgG抗体。三糖8是复合糖4的糖基部分,具有很强的免疫原性。