Work

Development of Noviomimetics as C-Terminal Hsp90 Inhibitors

Year: 2015

Type: article

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.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.5b00331

Authors: Mercy Anyika, Mason McMullen, Leah K. Forsberg, Rick T. Dobrowsky, Brian S. J. Blagg

Institution: University of Kansas

Language: English

Topic: Heat shock proteins research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke