KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Medicinal Chemistry
    • Medicinal Chemistry Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Medicinal Chemistry
    • Medicinal Chemistry Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Structure-Activity Relationships in Nucleotide Oligomerization Domain-1 (Nod1)-Agonistic γ-Glutamyl-diaminopimelic Acid Derivatives

    Thumbnail
    View/Open
    Agnihotri_2011.pdf (1.267Mb)
    Issue Date
    2011-03-10
    Author
    Agnihotri, Geetanjali
    Ukani, Rehman
    Malladi, Subbalakshmi S.
    Warshakoon, Hemamali J.
    Balakrishna, Rajalakshmi
    Wang, Xinkun
    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/jm101535e.
    Metadata
    Show full item record
    Abstract
    N-acyl-γ-glutamyl-diaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C12-γ-D-Glu-DAP. Analogues with glutaric or γ-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopimelic acid, L- or D-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the D-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic, but active analogues. Transcriptomal profiling showed a dominant upregulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds, and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1- and TLR-agonists, and are likely to be useful in designing vaccine adjuvants.
    URI
    http://hdl.handle.net/1808/23625
    DOI
    https://doi.org/10.1021/jm101535e
    Collections
    • Medicinal Chemistry Scholarly Works [225]
    Citation
    Agnihotri, G., Ukani, R., Malladi, S. S., Warshakoon, H. J., Balakrishna, R., Wang, X., & David, S. A. (2011). Structure-Activity Relationships in Nucleotide Oligomerization Domain-1 (Nod1)-Agonistic γ-Glutamyl-diaminopimelic Acid Derivatives. Journal of Medicinal Chemistry, 54(5), 1490–1510. http://doi.org/10.1021/jm101535e

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    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
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    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
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps