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Amino Acids. 2016 May;48(5):1319-29. doi: 10.1007/s00726-016-2190-7. Epub 2016 Feb 13.

6-(4-Amino-2-butyl-imidazoquinolyl)-norleucine: Toll-like receptor 7 and 8 agonist amino acid for self-adjuvanting peptide vaccine.

Author information

1
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki, Suzuka, Mie, 513-8670, Japan. yfujita@suzuka-u.ac.jp.
2
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki, Suzuka, Mie, 513-8670, Japan.

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.

KEYWORDS:

Adjuvant; Amino acid; Imidazoquinoline; Self-adjuvanting peptide vaccine; Toll-like receptor

PMID:
26874701
DOI:
10.1007/s00726-016-2190-7
[Indexed for MEDLINE]

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