Uniwersytet Medyczny w Lublinie

Program SMALL GRANT SCHEME

THE NATIONAL CENTRE FOR RESEARCH AND
THE POLISH-NORWEGIAN RESEARCH PROGRAMME
IMPLEMENTED UNDER THE NORWEGIAN FINANCIAL MECHANISM 2009-2014

Project tile:
Study of the Drug-REceptor interactions by selective CHromatographic columns with β2 adrenergic and GPR55 receptors immobilized onto a stationary phase.

Project Acronym:

DREnCH

Principal Investigator:

dr hab. n. farm. Anita Płazińska

e-mail: anita.plazinska@umlub.pl

Place of project implementation:
Laboratory of Medicinal Chemistry and Neuroengineering
Faculty of Pharmacy with Medical Analytics Division
Medical University of Lublin, W. ChodzkiStreet, 4a, 20-093 Lublin, Poland

Project duration:

1.09.2013 – 31.08.2015

Project summary:
Studying the mechanisms of the drug-receptor interactions is currently a very important issue in the field of medicinal chemistry. There are several experimental methods which allow to gain insight into the molecular details of interactions between molecule of drug and its molecular target and to determine the affinity of the compound (drug) toward the given receptor. One of such methods is the widely applied affinity chromatography which is based on specific interaction between an analyte (drug) and its molecular target (receptor immobilized on the stationary phase), Fig. 1.
 

Fig. 1. The scheme of the immobilized G protein-coupled receptor chromatographic stationary phases.

The main aim of this project is to study the ligand–receptor interactions using newly developed and selective screening technique. To achieve this goal the selective cellular membrane affinity chromatography columns (CMAC columns) with β2 adrenergic receptor (β2-AR) and GPR55 immobilized onto a stationary phase will be obtained, Fig. 2.
 

Fig. 2. The CMAC column.

β2-AR and GPR55 belong to the G-protein coupled receptors (GPCRs). GPCRs are very important targets for pharmacological intervention and approximately 40% of currently used drugs are directed toward them. β2-AR is a molecular target of the drugs which are used in the treatment of respiratory system. Another interesting molecular target is the recently discovered GPR55 receptor which is implicated in neuropathic and inflammatory pain, treatment of the osteoporosis, cell growth, and cell death. GPR55 is a promising new important cancer therapeutic target [1]. Thus, delineating the pharmacology of GPR55 and the discovery of selective antagonists merits further study and could lead to new therapeutics.

The resulting columns will be used to determine the affinities of tested compounds toward receptors (β2-AR, GPR55). This project creates an unique opportunity to develop new tools for rapid and precise screening for novel bioactive compounds of β2-AR and GPR55 in complex mixtures. The significant scientific impact of this project will be the progress in a rational, drugs design, based on the knowledge of the biological targets [1,2].

Literature:

1. Paul RK, Wnorowski A, Gonzalez-Mariscal I, Nayak SK, Pajak K, Moaddel R, Indig FE, Bernier M, Wainer IW. (R,R′)-4′-methoxy-1-naphthylfenoterol targets GPR55-mediated ligand internalization and impairs cancer cell motility. Biochem Pharmacol. 2014 Feb 15;87(4):547-61.
2. Plazinska A, Pajak K, Rutkowska E, Jimenez L, Kozocas J, Koolpe G, Tanga M, Toll L, Wainer IW, Jozwiak K. Comparative molecular field analysis of fenoterol derivatives interacting with an agonist-stabilized form of the β₂-adrenergic receptor. Bioorg Med Chem. 2014 Jan 1;22(1):234-46.

Objective and thematic areas of the Programme are available on the NCBR webpage: www.ncbir.pl/en/norwaygrants.

This project is funded / co-funded from Norway Grants in the Polish-Norwegian Research Programme operated by the National Centre for Research and Development.