Conformationally rigid histone deacetylase inhibitors correct DF508-CFTR protein function

Publication: Research - peer-reviewConference article – Annual report year: 2012

Documents

  • Author: Vickers, Chris J.

    La Jolla Institute for Allergy & Immunology

  • Author: Olsen, Christian Adam

    Organic Chemistry, Department of Chemistry, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Hutt, Darren M.

    La Jolla Institute for Allergy & Immunology

  • Author: Montero, Ana

    La Jolla Institute for Allergy & Immunology

  • Author: Leman, Luke J.

    La Jolla Institute for Allergy & Immunology

  • Author: Maryanoff, Bruce E.

    La Jolla Institute for Allergy & Immunology

  • Author: Balch, William E.

    La Jolla Institute for Allergy & Immunology

  • Author: Ghadiri, M. Reza

    La Jolla Institute for Allergy & Immunology

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Histone deacetylase (HDAC) inhibitors have shown partial efficacy toward correcting cystic fibrosis transmembrane conductance regulator (CFTR) protein function in ΔF508- CFTR models. While current treatment options for CF generally concentrate on disease symptoms such as management of inflammation and bacterial infection, therapy using HDAC inhibitors has the potential to treat and correct the underlying etiology associated with the disorder. Subsequently, we have synthesized conformationally well-defined cyclic tetrapeptide derivatives based on the natural product HDAC inhibitor Apicidin, in order to formulate a pharmacophore model to describe and enhance the bioactivity of these molecules. Through this study we have developed HDAC inhibitors which improve CFTR trafficking from the endoplasmic reticulum (ER) while ultimately increasing ion conductance across the plasma membrane of a lung epithelial cell line expressing ΔF508-CFTR.
Original languageEnglish
JournalABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Publication date2011
Volume242
PagesMEDI 293
ISSN0065-7727
StatePublished

Conference

Conference242nd National Meeting of the American-Chemical-Society (ACS)
Number242
CountryUnited States
CityDenver, CO
Period28/08/1101/09/11
Internet addresshttp://cen.acs.org/articles/89/i26/242nd-ACS-National-Meeting.html
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