Henrik Johansson
PhD student
Curriculum vitae
Education and Employment
Nov. 2010 – (Nov. 2013)
PhD-student, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark
Project: Design and synthesis of the first selective ligands for the GPRC6A-receptor: A novel human G-protein-coupled receptor with unknown physiological function
June 2010 – Oct. 2010
Research scientist, SPAGO Imaging AB, Lund, Sweden
Organic synthesis in research for novel MRI contrast agents
Sep. 2008 - June 2010
Lund University, Lund, Sweden
M.Sc. Programme – Organic Chemistry
Jan. 2010 – June 2010
Active Biotech AB, Lund, Sweden
M.Sc. Thesis project
Thesis title: Towards novel inhibitors of malarial Dihydroorotate Dehydrogenase – Synthesis of 2-aryl-6-methyl-pyrano[4,3-b]-pyrrol-4(1H)-ones and 4-(phenylamino)coumarin.
Sep. 2008 – June 2009
The University of Hong Kong, Hong Kong, China S.A.R.
Exchange studies within M.Sc. and B.Sc. degrees.
Sep. 2005 – June 2008
Lund University, Lund, Sweden
B.Sc. Programme – Chemistry
Mar. 2008 – June 2008
Chalmers University of Technology/ Södra Skogsägarna, Gothenburg, Sweden
B.Sc. Project
Thesis title: Ionic liquids as solvents in polysaccharide Functionalization – A study of cationic cellulose and Xylan derivatives
May 2003 – present
Kvarnen i Knällsberg HB
Co-founder and partner
Family-owned Café-, Bed- & Breakfast-, Conference-, and Events-business.
Project Outline
Design and synthesis of the first selective ligands for the GPRC6A-receptor: A novel human G-protein-coupled receptor with unknown physiological function
GPRC6A is the newest member of the human family C GPCRs, containing the characteristic large extracellular Venus-flytrap domain (VFT, Figure 1), a cysteine-rich region (CRD), a 7-trans-membrane (7TM) domain and an intracellular C-terminal. First[1] cloned in our group in 2004, it was deorphanized[2] as a promiscuous l-amino acid sensing receptor with preference for basic amino acids. Modelling and mutagenesis studies have demonstrated that basic amino acids bind to an orthosteric binding site in the VFT. GPRC6A is expressed in a wide number of tissues, including taste tissue, pancreatic islets, skeletal muscles, bone and liver tissues, which has lead to several hypotheses concerning its physiological function. [3][4]
- Figure 1. Model of a dimeric family C GPCR in its resting (left) and active state (right). The two states are in equilibrium with each other, shifted by the binding of natural ligands, agonists, or antagonists.
This work is focused on the synthesis of allosteric modulators for GPRC6A. Potent and selective ligands would be of great value as pharmacological tools in vitro and in vivo, for elucidating the receptors physiological function and possible relation to pathophysiology. This is highly relevant as 40-50% of all marketed drugs modulate GPCR-mediated processes.[5]
- Figure 2. Lead discovery by chemogenomics and medicinal chemistry led to the finding of antagonists (2) and (3).
Using a chemogenomic[6] approach we have identified 3-substituted 2-phenyl-indoles (1) (Figure 2) as allosteric modulators, binding to the 7TM-domain of GPRC6A. Synthesis routes to provide (2) and (3) as well as a wide range of analogues have been developed, and a thorough structure-activity relationship study is currently underway, aiming at generating more selective and potent modulators of the GPRC6A in the near future.
References:
- Wellendorph, P., Bräuner-Osborne, H., Gene, 2004, 335, 37-46
- Wellendorph, P., Hansen, K.B., Balsgaard, A., Greenwood, J.R., Egebjerg, J., Bräuner-Osborne, H., Mol. Pharmacol., 2005, 67 (3), 589- 597
- Pi, M., Zhang, L., Lei, S.-F., Huang, M.-Z., Zhu, W., Zhang,J., Shen, H., Deng, H.-W., Quarles, L.D., Journal of Bone and Mineral Research, 2010, 25 (5), 1092-1102
- Wellendorph, P. Johansen, L. D., Bräuner-Osbourne, H., Molecular Pharmacology of Promiscous Seven Transmembrane Receptors Sensing Organic Nutrients, Mol. Pharmacol. 2009, 76 (3), 453-465
- Allen, J.A., Roth, R.L., Annu. Rev. Pharmacol. Toxicol., 2011, 51, 117-144
- Harris, C.J., Stevens, A.P., Drug Discovery Today, 2006, 11 (19/20), 880-888
Publications
Fritzson, I., Johansson, H., Bedingfield P.T.P., P. Sundin, A., McConkey, G., J. Nilsson, U., The Discovery of Potent and Selective Malarial DHODH Inhibitor Compounds Based on 4-Aminocoumarin and 4-Aminopyran-2-one Scaffolds, Manuscript in Preparation.
Popular Science
Johansson, H., Bøgeløv Jørgensen, T., Gloriam, D.E., Wellendorph, P., Johansen, L.D., Sejer Pedersen, D., Bräuner-Osborne, H., Receptoren set fra lægemiddelstoffets synspunkt, Dansk Kemi, In Press.
Presentations
Johansson, H., Bräuner-Osborne, H., Sejer Pedersen, D., Taming the G-Protein Coupled Receptor GPRC6A, Oral Presentation, TOKS XII, Copenhagen, Denmark, September 2011.
Johansson, H., Bräuner-Osborne, H., Sejer Pedersen, D., Taming the G-Protein Coupled Receptor GPRC6A, Poster Presentation, ULLA Summer School, Parma, Italy, July 2011.
Scholarships and grants
April 2011
Niels Bohr Fondet
The Royal Danish Academy of Sciences and Letters
Financial support for the attendance at a scientific conference in Cambridge, UK, 2011
2008-2010
Several scholarships related to the M.Sc. studies and exchange studies including:
Stiftelsen Markussens Studiefond (2 times)
Stiftelsen Magnat-Jubel-stipendiistiftelsen
Stiftelsen Lunds Stads Jubileumsfond
Stiftelsen Mamsell M.C. Wollins donation (2 times)
2004
The Rotary Association Scholarship for study Excellence
Contact
Department of Medicinal Chemistry
Faculty of Pharmaceutical Sciences
University of Copenhagen
Universitetsparken 2
2100 Copenhagen
Denmark
Phone: (+45) 353 36257
Fax: (+45) 35 33 60 41
E-mail: hej(at)farma.ku.dk
Building 30, Room 325
