title: 6-(4-Amino-2-butyl-imidazoquinolyl)-norleucine: Toll-like receptor 7 and 8 agonist amino acid for self-adjuvanting peptide vaccine.
abstract: Generally, small peptides by themselves are weak to induce antibody responses. Toll-like receptor (TLR) ligands are attractive candidates of vaccine adjuvants to improve their antigenicity. The covalent conjugation of TLR ligands with antigens to produce self-adjuvanting peptide vaccine is a promising approach. Based on the structure of TLR7/8 ligands, a series of synthetic amino acids 6-imidazoquinolyl-norleucines were synthesized, wherein an imidazoquinoline structure as the TLR7/8 agonistic pharmacophores was constructed on the ε-NH2 group of Lys. Of them, 6-(4-amino-2-butyl-imidazoquinolyl)-norleucine showed the most potent TLR7 and TLR8 agonistic activities with EC50 values of 8.55 and 106 μM, respectively. Subsequently, mice were immunized with the influenza A virus M2e antigen mixed with or covalently conjugated to the TLR7/8 agonist amino acid, which led to induction of M2e specific antibody productions in the absence of other adjuvant. We successfully developed a novel efficient tool for self-adjuvanting peptide vaccines targeting TLR7/8.
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki, Suzuka, Mie, 513-8670, Japan. yfujita@suzuka-u.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki, Suzuka, Mie, 513-8670, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki, Suzuka, Mie, 513-8670, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki, Suzuka, Mie, 513-8670, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D006801:Humans; D007114:Immunization; D051379:Mice; D009646:Norleucine / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051200:Toll-Like Receptor 8 / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D022223:Vaccines, Subunit; D009646:Norleucine
keywords: Adjuvant; Amino acid; Imidazoquinoline; Self-adjuvanting peptide vaccine; Toll-like receptor