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    Toll-Like Receptor (TLR)-7 and -8 Modulatory Activities of Dimeric Imidazoquinolines

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    Shukla_2012.pdf (1.449Mb)
    Issue Date
    2010-02-09
    Author
    Shukla, Nikunj M.
    Mutz, Cole A.
    Malladi, Subbalakshmi S.
    Warshakoon, Hemamali J.
    Balakrishna, Rajalakshmi
    David, Sunil A.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm2010207.
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    Abstract
    Toll-like receptors (TLRs) are pattern recognition receptors that recognize specific molecular patterns present in molecules that are broadly shared by pathogens, but are structurally distinct from host molecules. The TLR7-agonistic imidazoquinolines are of interest as vaccine adjuvants given their ability to induce pronounced Th1-skewed humoral responses. Minor modifications on the imidazoquinoline scaffold result in TLR7-antagonistic compounds which may be of value in addressing innate immune activation-driven immune exhaustion observed in HIV. We describe the syntheses and evaluation of TLR7 and TLR8 modulatory activities of dimeric constructs of imidazoquinoline linked at the C2, C4, C8, and N1-aryl positions. Dimers linked at the C4, C8 and N1-aryl positions were agonistic at TLR7; only the N1-aryl dimer with a 12-carbon linker was dual TLR7/8 agonistic. Dimers linked at C2 position showed antagonistic activities at TLR7 and TLR8; the C2 dimer with a propylene spacer was maximally antagonistic at both TLR7 and TLR8.
    URI
    http://hdl.handle.net/1808/23634
    DOI
    https://doi.org/10.1021/jm2010207
    Collections
    • Medicinal Chemistry Scholarly Works [244]
    Citation
    Shukla, N. M., Mutz, C. A., Malladi, S. S., Warshakoon, H. J., Balakrishna, R., & David, S. A. (2012). Toll-Like Receptor (TLR)-7 and -8 Modulatory Activities of Dimeric Imidazoquinolines. Journal of Medicinal Chemistry, 55(3), 1106–1116. http://doi.org/10.1021/jm2010207

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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