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Research Article

Therapeutic Inhibition of Pro-Inflammatory Signaling and Toxicity to Staphylococcal Enterotoxin B by a Synthetic Dimeric BB-Loop Mimetic of MyD88

  • Teri L. Kissner,

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Gordon Ruthel,

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Shahabuddin Alam,

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Enrique Mann,

    Affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America

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  • Dariush Ajami,

    Affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America

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  • Mitra Rebek,

    Affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America

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  • Eileen Larkin,

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Stefan Fernandez,

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Robert G. Ulrich,

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Sun Ping,

    Affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, United States of America

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  • David S. Waugh,

    Affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, United States of America

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  • Julius Rebek Jr,

    Affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, United States of America

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  • Kamal U. Saikh mail

    kamal.saikh@amedd.army.mil

    Affiliation: Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America

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  • Published: July 27, 2012
  • DOI: 10.1371/journal.pone.0040773

About the Authors

Teri L. Kissner, Gordon Ruthel, Shahabuddin Alam, Eileen Larkin, Stefan Fernandez, Robert G. Ulrich, Kamal U. Saikh
Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America
Enrique Mann, Dariush Ajami, Mitra Rebek
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America
Sun Ping, David S. Waugh, Julius Rebek Jr
Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, United States of America

Corresponding Author

Email: kamal.saikh@amedd.army.mil

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: Performed cytokine measurement and micro-array experiments: TLK. Partly involved in writing the manuscript: TLK. Performed the confocal image data collection and edited the manuscript: GR. Performed the transfection, co-immunoprecipitation and animal experiments: SA. Contributed in the synthesis of compounds: EM DA. Contributed optimization and data analysis of micro-array based binding experiments: EL SF RU. Contributed design and synthesis of BB-loop mimetic: MR. Contributed expression and purification of TIR domain recombinant protein: SP DSW. Designed and supervised overall synthetic chemistry: JR. Designed and supervised the research and wrote the manuscript: KUS. Performed the experiments: TLK GR SA EM DA EL SF SP KUS. Analyzed the data: TLK GR SA EM DA MR EL SF SP DSW JR KUS. Contributed reagents/materials/analysis tools: RGU. Wrote the paper: TLK SP MR KUS.