A Clickable Oxysterol Photolabel Retains NMDA Receptor Activity and Accumulates in Neurons

Daniel M. Chen, Luke Ziolkowski, Ann Benz, Mingxing Qian, Charles F. Zorumski, Douglas F. Covey, Steven Mennerick

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Oxysterol analogs that modulate NMDA receptor function are candidates for therapeutic development to treat neuropsychiatric disorders. However, the cellular actions of these compounds are still unclear. For instance, how these compounds are compartmentalized or trafficked in neurons is unknown. In this study, we utilized a chemical biology approach combining photolabeling and click chemistry. We introduce a biologically active oxysterol analog that contains: (1) a diazirine group, allowing for the permanent labeling of cellular targets, and (2) an alkyne group, allowing for subsequent in situ visualization using Cu2+ catalyzed cycloaddition of an azide-conjugated fluorophore. The physiological properties of this analog at NMDA receptors resemble those of other oxysterols, including occlusion with other oxysterol-like compounds. Fluorescent imaging reveals that the analog accumulates diffusely in the cytoplasm of neurons through an energy-independent mechanism. Overall, this work introduces a novel chemical biology approach to investigate oxysterol actions and introduces a tool useful for further cell biological and biochemical studies of oxysterols.

Original languageEnglish
Article number923
JournalFrontiers in Neuroscience
StatePublished - Dec 6 2018


  • NMDA receptor
  • click chemistry
  • modulation
  • oxysterol
  • photolabel


Dive into the research topics of 'A Clickable Oxysterol Photolabel Retains NMDA Receptor Activity and Accumulates in Neurons'. Together they form a unique fingerprint.

Cite this