An Agonist/Antagonist Photo‐Switchable Vitamin D Mimetic Enables Bidirectional Optical Control of VDR
Abstract
ABSTRACT The secosteroid vitamin D (vitD) is essential for human health, maintaining bone metabolism, calcium homeostasis, and immune function via the vitamin D receptor (VDR). VDR activation has complex and cell‐specific effects in multiple tissues and spatial control of VDR activity is desirable. Here, we developed vitD mimetics bearing a photo‐switchable azobenzene motif to achieve spatiotemporal resolution in VDR activation. Structure‐guided tuning of regiochemistry and H‐bonding motifs provided a potent and selective vitD mimetic that can be reversibly switched in cellulo between agonist and antagonist states with light. In a model of osteogenesis, this unique bidirectional precision tool mediated light‐dependent osteogenic and osteolytic effects.
Article Details
Authors (12)
Xiu Ge
Department of Pharmacy Ludwig‐Maximilians‐University (LMU) Munich Munich Germany
Sabine Willems
Department of Pharmacy Ludwig‐Maximilians‐University (LMU) Munich Munich Germany
Francesco Melfi
Department of Pharmacy Ludwig‐Maximilians‐University (LMU) Munich Munich Germany
Tufan Mukhopadhyay
Department of Chemistry New York University New York New York USA
Johannes Morstein
Department of Chemistry New York University New York New York USA
Jordan Artzy
Department of Chemistry University of Pennsylvania Philadelphia Pennsylvania USA
Loris Knümann
Department of Pharmacy Ludwig‐Maximilians‐University (LMU) Munich Munich Germany
Giorgia Sbriccoli
Department of Pharmacy Ludwig‐Maximilians‐University (LMU) Munich Munich Germany
Jörg Pabel
Department of Pharmacy
Julian A. Marschner
Department of Pharmacy Ludwig‐Maximilians‐University (LMU) Munich Munich Germany
Dirk Trauner
P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry
Daniel Merk
Pharmaceutical Chemistry, Department of Pharmacy