title: Synthesis and immunoregulatory activities of conjugates of a Toll-like receptor 7 inert ligand.
abstract: In the synthesis and modification of the analogs of an adenine type of Toll-like receptor (TLR) 7 agonists, we found a special compound, 9-propionyloxy-8-hydroxy-2-(2-methoxyethoxy)-adenine (6). It is a synthesized TLR7 inert ligand, which does not respond to TLR7 itself. However, it can be coupled with protein or peptide antigens via propionyloxy functional group to promote their immunogenicity significantly. The compound was covalently coupled to protein and peptide to get the conjugates. The inductivity of cytokine production by the conjugates was 872.4-fold compared with the unconjugated antigens in vitro by mouse splenocyte. These data show that the immunostimulatory activity of inert TLR7 ligand can be endowed, and the activity of antigens can be amplified by conjugation with various proteins and peptides, thus broadening the potential therapeutic application and reducing the risk of TLR7 agonists' side effects.
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China; Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Gao
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Fangshu
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China; Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: wqjiang@szu.edu.cn.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Shenzhen University Cancer Research Center, Institute of Otorhinolaryngology, Shenzhen 518060, China. Electronic address: gyjin@szu.edu.cn.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D008024:Ligands; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D008024:Ligands; D051199:Toll-Like Receptor 7; D000225:Adenine
keywords: Adenine derivatives; Inert ligand; Innate immune response; Toll-like receptor