HYBRID EVENT: You can participate in person at Baltimore, Maryland, USA or Virtually from your home or work.

10th Edition of International Conference on Neurology and Brain Disorders

October 21-23, 2024

October 21 -23, 2024 | Baltimore, Maryland, USA
INBC 2018

Karol S. Bruzik

Speaker at Brain Disorders Conference - Karol S. Bruzik
The University of Illinois at Chicago, United States
Title : Toward selective modulators of GABA-A receptors


Heteropentameric GABA-A receptor is a principal drug target whose function is allosterically modulated by general anesthetics, sedatives and anticonvulsants, such as propofol, etomidate, barbiturates and neurosteroids. The current clinically used general anesthetics have numerous disadvantages including low potency, low receptor-type selectivity among the various Cys-loop receptors, low receptor isoform selectivity and resulting therefrom low therapeutic indices. Determining the locations and structures of modulator sites and the mechanisms that trigger conformational changes to the receptor is essential to the design and development of the next generation of these drugs.  The approach presented here garners this information using chemical synthesis of analogs of the general anesthetic drugs equipped with small photoactivatable residues such as a diazirine or an azide, characterization of the pharmacology of the new agents to verify the identity of their binding sites with those of the original drugs, photolabeling of a specific molecular isoform of the receptor, and performing Edman sequencing of the photolabeled fragments of the receptor to determine the position of modification.  Using this approach, binding sites of etomidate, propofol, barbiturate and neurosteroids have been determined.  Overall, a general picture emerges where agents belonging to the four different classes mentioned above bind to disparate regions of the receptor protein. 


Karol Bruzik received his BSc degree (1972) from the Technical University of Lodz, Poland, and his PhD (1980) and DSc (1987) degrees from Polish Academy of Sciences. After postdoctoral work at The Ohio State University (1981-83 and 1990-93) he joined the Department of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago as Assistant Professor, and is now Professor and Associate Head for Curriculum.  He is an author of more than 100 peer review publications in the area of organic and bioorganic chemistry, enzyme mechanisms, phosphoinositide signaling and allosteric modulators of ligand-gated ion channels, with emphasis on GABAA receptors.