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Synthesis and structure‐activity relationship of new cationic lipid derivatives
Author(s) -
Caroyez Benjamin,
Lonez Caroline,
Ruysschaert JeanMarie,
Jabin Ivan,
Vandenbranden Michel
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.803.9
Subject(s) - cationic polymerization , chemistry , amidine , amine gas treating , agonist , ligand (biochemistry) , tlr4 , structure–activity relationship , receptor , stereochemistry , medicinal chemistry , biochemistry , organic chemistry , in vitro
DiC14‐amidine is a cationic lipid that activates Toll‐like Receptor 4 (TLR4), which recognizes lipopolyssacharides. Apart from the presence of hydrocarbon chains, these ligands have so few similarities in terms of size and charge, they are therefore likely to activate the receptor via different mechanisms. Moreover, the role played by the different structural domains of diC14‐amidine remains largely unknown. Therefore, we synthesized a family of derivatives in order to assess the effect of their modifications on TLR4 agonist activity. We observed that a compound containing two non‐natural C13 chains has the highest activity, while an aliphatic chain length of more than 14 carbons has no activation. These results are consistent with the fact that lipopolysaccharides bearing C12 or C14 chains exhibit better TLR4 activity. We showed that a compound for which the secondary amine has been replaced by a methylene group loses all TLR4 activity, suggesting the importance of the amine in the recognition of the ligand. B. Caroyez is recipient of a FRIA fellowship, C. Lonez is a Postdoctoral Researcher (Wiener‐Anspach Foundation) and M. Vandenbranden is a Research Associate at the Belgian Fund for Scientific Research F.R.S./FNRS