VCU news

By Mary Kate Brogan
School of Pharmacy

A chemical designed by Youzhong Guo, Ph.D., an associate professor in the Department of Medicinal Chemistry in the Virginia Commonwealth University School of Pharmacy, has been launched on the market.

The chemical, called CHEAPS, maintains both the biochemical properties of cholesterol and the balance of hydrophobic – water-repellent – and hydrophilic – water-attracting – properties necessary for protein and cholesterol interaction research.

Guo and his team created this molecule, in part, due to their ongoing research on membrane proteins as drug targets. While conducting this research, Guo and his team discovered that existing chemicals on the market often had water solubility that was too high or too low for cholesterol research or that the existing chemicals did not keep the biochemical properties of cholesterol intact.

They needed a chemical that didn’t dissolve in water but could dissolve in other substances and also maintained the properties of cholesterol, so they created one. The team published a 2021 paper in Biochimica et Biophysica Acta (BBA) – General Subjects on the design, synthesis, characterization and application of CHEAPS.

Understanding the interactions between human membrane proteins and cholesterol is important in drug discovery and development, Guo said. More than 60% of current drugs on the market work by modulating membrane protein targets. In human cells, proteins – such as membrane proteins – typically make up about 50% of the composition by mass, while cholesterol and other lipids account for about 40%. An imbalance of the cholesterol/lipid ratio can lead to many human diseases, so understanding the interaction between proteins and lipids, such as cholesterol, is critical for understanding diseases and how to create drugs that properly target them.

CHEAPS will be a convenient research tool for those working on cholesterol-related research and may be used as a lead for new drug discoveries, Guo said.

“Better research tools, such as CHEAPS, can help us understand the structure and active mechanisms of many human membrane proteins,” Guo said. “Consequently, the advanced knowledge of membrane proteins will provide greater insights into what causes certain diseases/conditions and will create many possibilities to develop novel treatment strategies for membrane protein-related human diseases.”