title: Development of Noviomimetics as C-Terminal Hsp90 Inhibitors.
abstract: KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas , 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045-7563, United States.
authors.forename: Mercy
authors.initials: M
authors.lastname: Anyika
authors.affiliation: Department of Pharmacology and Toxicology Department, The University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Mason
authors.initials: M
authors.lastname: McMullen
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas , 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045-7563, United States.
authors.forename: Leah K
authors.initials: LK
authors.lastname: Forsberg
authors.affiliation: Department of Pharmacology and Toxicology Department, The University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Rick T
authors.initials: RT
authors.lastname: Dobrowsky
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas , 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045-7563, United States.
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
keywords: C-terminal inhibition; Heat Shock Protein 70; Heat Shock Protein 90; neuroprotection; noviomimetics
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