Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IICT Campus, Hyderabad, 500007, India; UMR 7242 CNRS- Neuroimmunology & Peptide Therapy Team, University of Strasbourg, Biotechnology and cell signaling, Illkirch, France/Laboratory of excellence Medalis, Institut de science et d'ingénierie supramoléculaire (ISIS), 67000, Strasbourg, France.
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
Int Immunopharmacol. 2019 Sep;74:105684. doi: 10.1016/j.intimp.2019.105684. Epub 2019 Jun 12.
A focused library of novel mannosylated glycophospholipids was synthesized employing imidate coupling and H-phosphate phosphorylation methods. All novel glycophospholipids were evaluated for their receptor interactions by molecular docking studies. Docking studies revealed dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) specific interaction of the glycophospholipid ligand P4 acts, which was further confirmed by in vitro DC-SIGN expression on monocyte-derived dendritic cells (MoDCs). Further, in vitro and in vivo immunomodulatory activity among the six compounds (P1-P6) examined, compound P4 displayed good immunopotentiation and adjuvant properties as indicated by the induced cytokine expression and enhanced ovalbumin (OVA) specific antibody (IgG) titers. Phosphatidylinositol mannosides (PIMs) analogues in the present study enforced the immunomodulatory properties, truncating parent PIMs or tailor-made of PIMs may bring the novel efficacious molecules, which will be useful in vaccine preparation against different diseases.
采用亚氨酸酯偶联和 H-磷酸化方法合成了新型甘露糖基糖磷脂库。通过分子对接研究评估了所有新型糖磷脂的受体相互作用。对接研究表明，糖磷脂配体 P4 与树突状细胞特异性细胞间黏附分子-3 抓取非整联蛋白（DC-SIGN）的特异性相互作用，这进一步通过单核细胞衍生的树突状细胞（MoDC）上的体外 DC-SIGN 表达得到证实。此外，在研究的六种化合物（P1-P6）中进行了体外和体内免疫调节活性测试，化合物 P4 表现出良好的免疫增强和佐剂特性，这表现为诱导细胞因子表达和增强卵清蛋白（OVA）特异性抗体（IgG）滴度。本研究中的磷酸肌醇甘露糖苷（PIMs）类似物增强了免疫调节特性，缩短亲本 PIMs 或定制 PIMs 可能会带来新型有效分子，这将有助于针对不同疾病的疫苗制备。
