新型 1,2,3-三氮唑键合 PamCAG 缀合物作为潜在的 TLR-2 激动型疫苗佐剂。
Novel 1,2,3-triazole-tethered PamCAG conjugates as potential TLR-2 agonistic vaccine adjuvants.
机构信息
Vaccine Immunology Laboratory, OSPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201 002, India.
Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi.
出版信息
Bioorg Chem. 2021 Jun;111:104838. doi: 10.1016/j.bioorg.2021.104838. Epub 2021 Mar 22.
A focused library of water soluble 1,2,3-triazole tethered glycopeptide conjugates derived from variety of azido-monosaccharides and aliphatic azido-alcohols were synthesized through manipulation at the C-terminus of PamCAG and screened for their potential as TLR2 agonistic adjuvants against HBsAg antigen. In vitro ligand induced TLR2 signal activation was observed with all the analogues upon treatment with HEK blue TLR2 cell lines. Conjugate derived from ribose (6e), which exhibited pronounced HBsAg specific antibody (IgG) titer also shown enhanced CD8+ population indicating superior cell mediated immunity compared to standard adjuvant PamCSK. Further, docking studies revealed ligand induced heterodimerization between TLR1 and 2. Overall, the result indicates the usefulness of novel conjugates as potential vaccine adjuvant.
通过对 PamCAG 的 C 末端进行操作，合成了一系列源于各种叠氮单糖和脂肪族叠氮醇的、具有水溶性 1,2,3-三唑键的糖肽缀合物的聚焦文库，并将其作为 TLR2 激动性佐剂对 HBsAg 抗原进行筛选。在体外，在用 HEK blue TLR2 细胞系处理所有类似物时，观察到配体诱导的 TLR2 信号激活。与标准佐剂 PamCSK 相比，来源于核糖（6e）的缀合物显示出明显的 HBsAg 特异性抗体（IgG）效价，也显示出增强的 CD8+群体，表明具有优越的细胞介导免疫。此外，对接研究表明配体诱导 TLR1 和 2 之间的异二聚化。总的来说，结果表明这些新型缀合物作为潜在疫苗佐剂的有用性。
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