Syntheses of fluorescent imidazoquinoline conjugates as probes of Toll-like receptor 7

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Shukla, Nikunj M.¹  Mutz, Cole A.¹  Ukani, Rehman¹  Warshakoon, Hemamali J.¹  Moore, David S.²  David, Sunil A.¹ 

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66047 USA

[2] Univ Kansas, Microscopy & Analyt Imaging Lab, Lawrence, KS 66045 USA

关键词: Imidazoquinoline;    Toll-like receptor;    TLR7;    Fluorescent probe;    Flow cytometry;   

DOI  :  10.1016/j.bmcl.2010.09.093

来源: Elsevier

【 摘 要 】

Toll-like receptor (TLR)-7 agonists show prominent immunostimulatory activities. The synthesis of a TLR7-active N-1-(4-aminomethyl)benzyl substituted imidazoquinoline 5d served as a convenient precursor for the covalent attachment of fluorophores without significant loss of activity. Fluorescence microscopy experiments show that the fluorescent analogues are internalized and distributed in the endosomal compartment. Flow cytometry experiments using whole human blood show differential partitioning into B, T, and natural killer (NK) lymphocytic subsets, which correlate with the degree of activation in these subsets. These fluorescently-labeled imidazoquinolines will likely be useful in examining the trafficking of TLR7 in immunological synapses. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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