Open AccessSynthesis and Characterization of a Diazirine-Based Photolabel of the Nonanesthetic Fropofol
Author(s) -
E. Railey White,
David Leace,
Victoria M. Bedell,
Natarajan V. Bhanu,
Benjamin A. García,
William P. Dailey,
Roderic Eckenhoff
Publication year - 2020
Publication title -
acs chemical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/acschemneuro.0c00667
Subject(s) - anesthetic , diazirine , propofol , chemistry , affinities , photoaffinity labeling , pharmacology , neuroscience , binding site , computational biology , stereochemistry , psychology , biology , medicine , biochemistry , anesthesia
The mechanisms of general anesthetics have been debated in the literature for many years and continue to be of great interest. As anesthetic molecules are notoriously difficult to study due to their low binding affinities and multitude of binding partners, it is advantageous to have additional tools to study these interactions. Fropofol is a hydroxyl to fluorine-substituted propofol analogue that is able to antagonize the actions of propofol. Understanding fropofol's ability to antagonize propofol would facilitate further characterization of the binding interactions of propofol that may contribute to its anesthetic actions. However, the study of fropofol's molecular interactions has many of the same difficulties as its parent compound. Here, we present the synthesis and characterization of ortho -azi-fropofol (AziF o ) as a suitable photoaffinity label (PAL) of fropofol that can be used to covalently label proteins of interest to characterize fropofol's binding interactions and their contribution to general anesthetic antagonism.