Recognition of nucleic acid ligands by toll-like receptors 7/8: importance of chemical modification.
Toll-like receptors 7 and 8 (TLR7/8), known as pattern recognition receptors (PRR), are currently viewed as important targets for the development of new therapies for multiple diseases. Therefore, manipulating the immune response by using TLR7/8 agonists or antagonists might be of therapeutic value. Nucleic acid-like structures are well-known TLR7/8 ligands, such as single-stranded RNA (ssRNA), small interfering RNA (siRNA), CpG-oligodeoxynucleotides (ODNs) and nucleoside analogues. However, these nucleic acid TLR7/8 ligands show a variety of pharmacological properties and change of their structures offers a high degree of diversity. Unnatural modified nucleosides have been explored to expand the properties and the applications of nucleic acid. In this regard, chemical modification of nucleosides is very useful for production of specific pharmacological qualities of nucleic acid TLR7/8 ligands. In this review, we will summarize the characteristics of nucleic acid TLR7/8 ligand system and describe the applications of chemical modifications, with a focus on potency and structure-activity relationships (SAR).
Department of Laboratory Centre, The Affiliated Tenth People's Hospital, Tongji University, Shanghai 200072, China.
Hui
H
Yu
Zhanli
Z
Wang
Gang
G
Sun
Yongchun
Y
Yu
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D009696:Nucleic Acids / Q000737:chemistry* / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*
D007155:Immunologic Factors; D009696:Nucleic Acids; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8