June 22, 2016
The College of Pharmacy Monthly Research Publication Highlight features a computational chemistry approach that reveals a potentially novel reaction pathway in the inactivation of the hunger hormone, Ghrelin.
The UK College of Pharmacy Research Publication Highlight for May 2016 is titled “Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of “hunger hormone” ghrelin” and was published in the Scientific Reports.
The project was conducted in the Molecular Modeling and Biopharmaceutical Center in the UK College of Pharmacy. The lead author on the study is Jianzhuang Yao, a postdoctoral fellow in the department of Pharmaceutical Sciences in the laboratory of Drs. Chang-Guo Zhan and Fang Zheng. Visiting scholar, Yaxia Yuan, also contributed to the project.
Ghrelin is a gut hormone that increases appetite in the extended hours following a meal. Thus, it is an interesting target for the development of novel anti-obesity drugs. Ghrelin is a small, peptide hormone that contains a fatty side chain in its active form. The removal of this acyl-group from the core peptide inactivates the hormone and decreases appetite. The Zhan and Zheng lab has been working with butyrylcholinesterase enzymes that are capable of breaking such bonds and have shown promise as biological therapeutics in the treatment of cocaine addiction and overdose. In the present study, the UK team used computational chemistry to determine if such enzymes could potentially mediate the inactivation of Ghrelin. Their results not only show that such a reaction is possible, but reveal a novel enzymology that has yet to be described for acylation-dependent hydrolysis.
“The findings of the present study are intriguing. Further studies will be required to determine if a biological, therapeutic approach to decreasing Ghrelin holds promise for the treatment of obesity” said Greg Graf, Assistant Dean for Translational Research.