| Title | Conjugation of weak ligands with weak antigens to activate TLR-7: A step toward better vaccine adjuvants |
| Authors | Gao, Dong Zeng, Juan Wang, Xiaodong Liu, Yu Li, Wang Flu, Yunlong Gao, Ningning Diao, Yuwen Wang, Zhulin Jiang, Wenqi Chen, Jinhua Jin, Guangyi |
| Affiliation | Shenzhen Univ, Canc Res Ctr, Shenzhen 518060, Peoples R China. Shenzhen Hornetcorn Biotechnol Co Ltd, Shenzhen 518045, Peoples R China. Peking Univ, Shenzhen Grad Sch, Lab Chem Genom, Lab Computat Chem & Drug Design, Shenzhen 518055, Peoples R China. Shenzhen Univ, Key Lab Optoelect Devices & Syst, Minist Educ, Coll Optoelect Engn, Shenzhen 518060, Peoples R China. |
| Keywords | Toll-like receptor Adenine derivative Adjuvant Immunostimulatory activity TOLL-LIKE-RECEPTORS POTENT INTERFERON INDUCERS INNATE IMMUNITY IMMUNOSTIMULATORY ACTIVITY SEPTIC SHOCK FORCE-FIELD PROTEIN TOLL-LIKE-RECEPTOR-7 RECOGNITION IMIDAZOQUINOLINES |
| Issue Date | 2016 |
| Publisher | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY |
| Citation | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY.2016,120,111-120. |
| Abstract | To study the structure-activity relationship (SAR) of Toll-like receptor 7 (TLR-7) agonists based on 8-oxoadenines, a novel subset of C9-substituted 8-hydroxy-2-(2-methoxyethoxy)-adenines and their antigen conjugates were synthesized. In vitro, the ability of cytokines (IL-12p70 and IFN-gamma) induction of ligands with alkyl acid at C9-position were very weak compared with benzoic acid counter parts. Unexpectedly, its antigen conjugates that conjugated with proteins or peptides with weak immunogenicity, showed enhanced activity of cytokines induction. After administered systemically in mice in vivo, all conjugates induced prolonged increase in pro-inflammatory cytokines and antigen-specific IgG levels in serum compared with free compounds. Results from molecular dynamics (MD) simulations further confirmed the conclusion and provided the details of interaction to explain the phenomenon of experiment. In conclusion, we discovered that TLR-7 could be activated via some conjugates of weak ligand and weak antigen, which could be safer adjuvant candidates for vaccines in the future. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/433699 |
| ISSN | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.04.070 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 深圳研究生院待认领 |
