Projects

"Click" Chemistry Magnetic Nanoparticles used for Purification and Enrichment of the CB2 Receptor for Characterization by Mass Spectrometry

Student: Dennis Szymanski
Department: Chemistry
Advisor: Alex Makriyannis

Abstract

The cannabinoid receptor belongs to the G-protein coupled receptor family. It is a typical seven-transmembrane receptor and therefore is a very hydrophobic protein. Due to its hydrophobicity it is very difficult to characterize the receptor and more specifically its 3-d binding domain. Traditional methods, such as X-ray crystallography, can’t be used due to the protein’s hydrophobicity. The most effective method of characterizing the receptor and its binding site is by computational methods and covalent probes, termed "Ligand Based Structural Biology". G-Protein coupled receptors are very important in the field of medicine. Expanding the knowledge of these hydrophobic receptors will lead to many benefits in the medicinal community.

Magnetic "Click" chemistry nanoparticles will be employed in order to purify and enrich the hydrophobic cannabinoid receptor sample. Click chemistry is a valuable and novel method for attaching the receptor to the nanoparticles through a covalent click chemisrty ligand that covalently binds to the receptor then "clicks" to the nanoparticle. Once bound to the magnetic nanoparticles a magnetic field will be applied to secure the sample while washing away other protein impurities. This also allows for enrichment of the sample to a desired concentration. This is extremely valuable for mass spectrometric analysis of low concentrated samples, and is an area of great interest for mass spec based proteomics.