knowledge improvement the of the 5-HT3 receptor

The 5-HT3 receptor is a member of the Cys-loop family of ligand gated ion channels and is involved in several different disease symptoms such as radiotherapy induced emesis and the irritable bowel syndrome. The goal of this project will be improving the knowledge of the 5-HT3 receptor binding site and the interactions involved in ligand binding.

Until now, a fragment library containing 1040 diverse fragments was screened against both the 5-HT3A receptor (partner 5) and the Ls-AChBP. As a result unique binders for both proteins are identified as well as several common binders. Next, close analogues of the identified hits were tested and a small series of compounds was designed and synthesized to improve understanding of the structure activity relation for these classes of compounds.

Parallel to this, homology modelling is utilized to create in silico models of the 5-HT3A receptor. The research involved here will focus mainly on mapping the specific interactions involved when a ligand binds to the human 5-HT3A receptor. For the 5-HT3A receptor homology models the AChBP crystal structures serve as templates.