Scaffold Hopping by “Fuzzy” Pharmacophores and its Application to RNA Targets

Authors

  • Yusuf Tanrikulu,

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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  • Manuel Nietert,

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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  • Ute Scheffer Dr.,

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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  • Ewgenij Proschak,

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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  • Kristina Grabowski,

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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  • Petra Schneider Dr.,

    1. Schneider Consulting GbR, George-C.-Marshall Ring 33, 61440 Oberursel, Germany
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  • Markus Weidlich,

    1. Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany
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  • Michael Karas Prof.,

    1. Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany
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  • Michael Göbel Prof. Dr.,

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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  • Gisbert Schneider Prof. Dr.

    1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Siesmayerstrasse 70, 60323 Frankfurt am Main, Germany, Fax: (+49) 69-798-24880
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Abstract

original image

Don't look sharp, look fuzzy. A technique for “fuzzy” pharmacophore screening is presented. Two prospective applications with RNA targets were performed: virtual screening for inhibitors of the Tat-TAR RNA interaction and in vitro protein expression. The hits contain alternative scaffolds and were found through a fuzzy pharmacophore model (see figure) of ligand binding poses.

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